Bleeding and Coagulation Catastrophes in the Operating Room

Key action points in the management of bleeding and coagulation catastrophes in the operating room include the following:

• Call for help, and request extra personnel
• Activate a massive blood transfusion protocol (if such a protocol has been established)
• Communicate closely with the surgical team
• Identify the source of bleeding, and try to achieve hemostasis as soon as possible, either temporarily or permanently
• Obtain large, secure intravenous (IV) accesses and a rapid infusion system
• Continuously monitor vital signs; consider invasive hemodynamic monitoring
• Frequently monitor hemoglobin level and coagulation status
• Ensure the accuracy of the blood-checking process
• Detect and treat complications of massive blood transfusion (eg, hypothermia, dilutional coagulopathy, transfusion-related cardiac overload, transfusion-related acute lung injury, and hypocalcemia and other electrolyte disturbances) as early as possible
• Consider administration of recombinant coagulation factors and non–blood product hemostatic agents

Massive hemorrhage, defined as blood loss in excess of one circulating volume within a 24-hour period, is a major cause of mortality after trauma or surgery. The pathophysiology of massive blood loss is complex, comprising a wide range of physiologic derangements arising from tissue injury, bleeding, and transfusion of blood or blood products. Injury to body parts activates several systems, including the autonomic nervous system, the coagulation system, the fibrinolytic system, the complement system, and the systemic inflammatory response. ^{[1, 2, 3]} Accordingly, massive blood loss is not corrected by simply replacing what was lost via blood transfusion.

The most important step in managing bleeding during surgery is maintaining adequate intravascular volume. This is especially true in the setting of cardiac or renal disease, where either hypervolemia or hypovolemia can create detrimental effects. Anemia is a direct effect of blood loss and must be treated to maintain adequate oxygen-carrying capacity.

Although the optimal hemoglobin threshold continues to be debated, maintaining a hemoglobin level of more than 6 g/dL is recommended. Maintaining a higher hemoglobin level (>7 g/dL) may be indicated if there is a history of cardiovascular or cerebrovascular disease.

As blood loss continues, coagulopathy, either consumptive or dilutional, will become evident. Hyperfibrinolysis destroys stable blood clots, and antifibrinolytic agents may be required.

Transfusion of blood and blood products is usually necessary during a bleeding catastrophe. The process of ordering and checking blood may be cumbersome during massive blood transfusion. Accordingly, it may be advisable to assign a dedicated staff member to focus on blood ordering and administration while the anesthesiologist is taking care of the patient. This may reduce the errors that may arise with multitasking during life-threatening conditions. 

Transfusion of blood and blood products is not without negative consequences. Blood transfusion mismatch is detrimental; it is most commonly caused by clerical error, which may be more likely to occur in emergency situations. Transfusion can also give rise to transfusion-associated circulatory overload ^[4] (TACO; see Case Example 3) and transfusion-related acute lung injury (TRALI). Rapid transfusion can cause hypothermia and hypocalcemia, which lead to impaired platelet function, impaired coagulation, arrhythmia, hypotension, and ventricular dysfunction. All of these will cause further bleeding and hypotension. 

If bleeding is persistent and prolonged, it may lead to tissue hypoxemia, severe acidosis, multiorgan dysfunction, or death.  

Addressing the problem

Anesthesiologists are well prepared to manage major bleeding and always anticipate that there may be a need to do so. Nevertheless, a considerable number of bleeding catastrophes arise in emergency settings or unusual circumstances. Understanding the physiology of massive hemorrhage, initiating massive transfusion, and preparing adequate blood inventories are fundamental components of management. The goal of treatment is to restore and maintain adequate oxygen-carrying capacity to the end organs.

Early detection is the first step. The importance of continuous vigilance cannot be overstated. Clear lines of communication with the surgical team regarding the surgical findings and the likelihood of obtaining hemostasis must be established, even when the surgeons are performing damage-control surgery. A massive transfusion protocol should be activated (if one exists at the institution), or the blood bank should be directly instructed to prepare for massive transfusion.

The assistance of additional practitioners can facilitate the processes of obtaining IV access, checking and transfusing blood, and sending blood for laboratory testing. To prevent hypothermia, IV fluid and blood should be warmed before being administered to the patient. A rapid infusion system can warm and administer IV fluid at rates as high as 1000 mL/min.

Frequent blood testing is necessary for early diagnosis of anemia or coagulopathy associated with blood loss and blood transfusion. However, the fixed transfusion ratio of packed red blood cells (PRBCs) to fresh frozen plasma (FFP) to platelets (PRBC:FFP:Plt) may be implemented to prevent severe dilutional coagulopathy and further blood loss during massive hemorrhage. Point-of-care (POC) tests such as thromboelastography (TEG) or thromboelastometry (TEM) can rapidly identify coagulopathic states, as well as suggest which blood components may be needed.  

Calcium replacement is usually needed to treat hypocalcemia during massive transfusion. Hyperkalemia, whether resulting from the potassium in stored PRBCs or from trauma, should be treated by administering insulin/glucose, sodium bicarbonate, or calcium chloride. Washed PRBCs can be used in hyperkalemia patients who require PRBC transfusion.

Anticoagulant use may worsen blood loss and may warrant administration of a reversal agent. Heparin can be reversed with protamine. If immediate reversal of warfarin is indicated, FFP or prothrombin complex concentrate (PCC) is recommended.

Novel oral anticoagulants (NOACs) are becoming increasingly popular because of their ease of use as compared with warfarin. In the event of life-threatening or uncontrolled bleeding, reversal of NOACs may be indicated. Idarucizumab is a specific reversal agent for dabigatran. Andexanet alfa (inactivated recombinant coagulation factor Xa) is a specific reversal agent for oral factor Xa inhibitors. ^[5]  This agent is currently approved for reversal of rivaroxiban and apixaban via accelerated approval from the US Food and Drug Administration (FDA).

In the event of uncontrolled bleeding from coagulopathy, recombinant or activated coagulation factors can play an important role. Several recombinant coagulation factors are commercially available.

Currently, the use of activated coagulation factors in surgical bleeding is an off-label indication. The coagulation factor concentrates that have been used to obtain surgical hemostasis are activated factor VII (FVIIa), three-factor or four-factor PCC, and anti-inhibitor coagulation complex.

FVIIa has been successfully used in the management of uncontrolled bleeding in trauma patients. ^{[6, 7]} At present, however, the data are still insufficient to support the generalized use of FVIIa for this indication.

The FDA-approved indication for PCCs is for rapid reversal of the effect of warfarin in adult patients with acute major bleeding. In massive blood loss, PCCs are administered to rapidly restore vitamin K–dependent coagulation factors. The recommended dose range is 25-50 U/kg, depending on the international normalized ratio (INR). The FDA has also issued a warning about arterial and venous thrombosis associated with PCC use. PCC is contraindicated in patients with disseminated intravascular coagulation (DIC). Some PCCs contain heparin and thus are contraindicated in patients with heparin-induced thrombocytopenia (HIT).

Evidence-based recommendations

Several professional organizations have published guidelines addressing massive hemorrhage and massive transfusion management, including the American Society of Anesthesiologists (ASA) ^[8] ; the American College of Surgeons (ACS) Committee on Trauma ^[9] ; the pan-European, multidisciplinary Task Force for Advanced Bleeding Care in Trauma ^[10] ; and the Joint United Kingdom Blood Transfusion Services Professional Advisory Committee (JPAC). ^[11] Although the guidelines necessarily differ from one other in some respects, there are some important and common recommendations that almost all of them share, such as the following:

• Establishment of a massive transfusion protocol among multidisciplinary groups within hospitals
• Early recognition of the bleeding episode and achievement of hemostasis
• Identification and, if applicable, reversal of the existing effect of anticoagulant(s)
• Establishment of a threshold for triggering a massive transfusion protocol and the use of a fixed-ratio (PRBC:FFP:Plt) transfusion protocol in emergency situations; consideration of transition to goal-directed transfusion ^[12] after laboratory results are obtained
• Identification and early treatment of coagulation abnormality (dilutional, consumptive, or fibrinolytic coagulopathy)
• Utilization of bedside POC testing; consideration of viscoelastic testing for identifying coagulopathy
• Detection and treatment of complications associated with massive hemorrhage and transfusion - Hypothermia, hypocalcemia, hyperkalemia, metabolic acidosis, TRALI, TACO, hemolytic transfusion reaction
• Establishment of a postoperative care pathway after massive hemorrhage and massive blood transfusion

Clinical scenario

An 80-year-old man undergoes coronary artery bypass grafting (CABG), mitral valve replacement, aortic valve replacement, and tricuspid valve repair under cardiopulmonary bypass (CPB). After separation from CPB, bleeding continues. Coagulation studies indicate severe coagulopathy. Bleeding continues to the point where one rapid infusion device is unable to keep up.

After correction of coagulopathy, the surgeon reports that there is no significant source of bleeding except from the suture line sites, but the blood clot, once formed, immediately dislodges from the bleeding sites instead of staying in place. 

Resolution

This is an uncommon scenario in which correction of medical coagulopathy does not translate into hemostasis. Whereas the clot was visualized by the surgeon at the surgical sites, there was continued oozing from various suture sites. Volume resuscitation and correction of coagulopathy were the keys to management in this case. Viscoelastic tests, such as TEG and rotational TEM (ROTEM), can be very helpful in goal-directed transfusion therapy.

This patient received a massive transfusion of blood products (including FFP, platelets, and cryoprecipitate), which led to dilutional anemia. PRBCs were transfused as needed. Coagulation studies showed a supranormal coagulation level. The decision was made to administer anti-inhibitor coagulation complex and apply pressure dressing on the heart and aorta. After this step was repeated a few times, hemostasis was obtained. 

Clinical scenario

A 28-year-old full-term pregnant woman with a history of previous cesarean section undergoes a repeat cesarean section under spinal anesthesia without sedation. After delivery, placenta accreta is found. The obstetrician decides to perform an emergency cesarean hysterectomy. 

Resolution

Placenta accreta is a condition in which the placenta grows deeply into uterine muscle and cannot be separated from the uterus after delivery. The presence of placenta within uterine tissue precludes effective uterine contraction, and bleeding from the uterus ensues. The decision to perform emergency hysterectomy is a very difficult one to make, but the procedure can be lifesaving in such cases.

The most important measure in this scenario is volume resuscitation. Invasive monitoring and the placement of additional large-bore central or peripheral venous catheters are necessary but should not delay volume resuscitation. Rapid blood transfusion at rates as high as 500 mL/min may be necessary.

The massive transfusion protocol was activated, and volume resuscitation was immediately started. A fixed-ratio transfusion protocol was used (PRBC:FFP:Plt = 6:6:10). A forced-air warming device and a blood warmer were used to maintain normothermia. Although the patient was initially nervous, she was eventually calmed without difficulty. She had lost about 3-4 L of blood in the first 10 minutes before the obstetricians were able to control the uterine arteries. She became mildly hypothermic but recovered after aggressive warming. The emergency hysterectomy was performed successfully. 

Clinical scenario

A 72-year-old woman with severe biventricular dysfunction undergoes CABG, aortic valve replacement, and tricuspid valve repair. After separation from CPB, significant bleeding is evident. Coagulation studies yield abnormal results. However, rapid transfusion would induce right ventricular failure despite maximal inotropic support. The surgeon still reports continuous bleeding with minimal blood clot formation and requests that additional blood products be given. 

Resolution

This scenario illustrates a common dilemma in blood transfusion: Whenever coagulation factors are transfused, fluid is also given. One of the complications from blood transfusion is TACO, defined as the development of symptoms or signs of volume overload (eg, acute dyspnea, high central venous pressure [CVP], high brain natriuretic peptide [BNP] level, heart failure, pulmonary edema, and positive fluid balance) within 6 hours of transfusion.

TACO is an especially important concern in patients with ventricular dysfunction who need blood or blood components but would be adversely affected by the fluid volume associated with their administration. The incidence of TACO is probably underreported but has been estimated to be approximately 1% after transfusion. The main components of treatment include immediate cessation or reduction of the rate of transfusion, provision of support for the cardiopulmonary system, and administration of diuretics.    

The patient received FFPs and platelets as tolerated, while filling pressure, intravascular volume, and cardiac status were closely monitored by means of transesophageal echocardiography (TEE). Furosemide was given to promote diuresis. With judicious transfusion that included plasma, platelets, and monitoring interventions, an optimal coagulation level was achieved, and the chest was then closed. 

Clinical scenario

A 62-year-old man presents with renal cell carcinoma that has metastasized into the inferior vena cava (IVC). He is scheduled for a right nephrectomy and removal of the IVC tumor. During IVC tumor removal, several major veins draining into the IVC are temporarily occluded by endovascular balloons to control the bleeding. Unfortunately, the patient is exsanguinating from profuse, uncontrolled blood loss. He experiences severe, prolonged hypotension that results in cardiac arrest.

Resolution

This scenario illustrates a true catastrophe from rapid, profuse, uncontrolled blood loss and underscores the importance of team management during a crisis.

The anesthesia team anticipated a major blood loss and had already secured central venous access via large-bore catheter. Several anesthesiologists and critical care nurses were called for help. A massive transfusion protocol was activated. Two rapid infusion system devices were utilized. The attending anesthesiologist took on the role of team leader and assigned individual team members to the following tasks:

• Blood checking and administration
• Medication management
• Charting and ordering
• TEE monitoring
• Managing the patient and communicating with the attending surgeon

TEE was used to assess intravascular volume as well as cardiac function. However, acute pulmonary edema developed, possibly from TRALI or severe ventricular dysfunction. Bleeding continued, and the patient expired.