Introduction

Understanding of coagulation and coagulopathy is essential to the practice of anesthesia. This begins with preoperative assessment and planning. A detailed history is the first step. Laboratory testing can reveal abnormalities that may have otherwise gone undetected, as many disorders are asymptomatic until unmasked by the stress of surgery. Some of these disorders may be inherited or acquired, and their presentation and treatment must be considered. Intimate familiarity of this topic allows the anesthesiologist to adequately prepare for coagulopathy and thrombotic events in the perioperative environment.

Coagulation begins with vascular endothelial injury. The first step in the coagulation cascade is platelet aggregation. After injury, exposed von Willebrand factor (vWF) binds to circulating platelets, resulting in platelet activation and thromboxane generation. Platelet activation results in conformational change, allowing for further binding of vWF and fibrinogen. As more circulating platelets become bound and activated, cross-linking of vWF and fibrinogen results in a platelet plug. The activated platelet surface, now as part of a stable structure, can allow for initiation of the humoral coagulation cascade [Reference Nguyen, DasGupta, Wahed and Cruz1].

When performing a preoperative assessment for a patient in whom you expect existing coagulopathy, or if there is an elevated risk of developing coagulation issues intraoperatively, it is important to focus on the patient’s bleeding and clotting history [Reference Nguyen, DasGupta, Wahed and Cruz1]. This is also crucial to discuss prior to surgery involving a significant degree of expected blood loss with a high likelihood of blood product transfusion. The anesthesiologist must conduct a thorough review of the patient’s medical and surgical history, and perform relevant parts of the physical examination, in addition to the standard components of a preoperative assessment. Questions regarding the patient’s family history and the presence of any coagulation disorders are also helpful, as some are inherited. It is important to include assessment for renal and hepatic dysfunction, as impairments in these organ systems may produce coagulopathy [Reference Nguyen, DasGupta, Wahed and Cruz1]. A thorough review of the patient’s medication list will reveal any nonsteroidal antiinflammatory drugs (NSAIDs) (including aspirin), antiplatelet therapy, or anticoagulation that may produce an elevated bleeding risk and potentially pose a contraindication to particular surgical procedures. Asking the patient about any prior history of blood transfusion is helpful in identifying an increased risk of antibodies to particular blood antigens. In some cases, patients may have rare antibodies that make it challenging to locate sufficient crossmatched blood. Standard laboratory tests (including, but not limited to, complete blood count (CBC), comprehensive metabolic panel (CMP), coagulation studies, type and screen (T+S)) may help to unmask some of these issues. It can also be useful to probe about bleeding history with particular questions that address bleeding disorders, outside the realm of our standard preoperative laboratory tests (ex: minor mucosal bleeding and von Willebrand’s disease (vWD)) [Reference Nguyen, DasGupta, Wahed and Cruz1].

Screening questions often start with the patient’s medical history, and should be directed at assessing whether the patient has any known coagulation disorders or any renal or hepatic dysfunction, whether there is a positive family history, and whether the patient has undergone any significant bleeding challenge in the past, including the results of that encounter. A patient with renal dysfunction (acute or chronic) may exhibit some degree of uremic platelet dysfunction. A patient suffering from end-stage liver disease (or fulminant hepatic failure) may exhibit coagulopathy in the form of deficient coagulation factor production and thrombocytopenia. Take note of any significant blood loss, especially requiring transfusion, during any prior routine procedures. The overall assessment of a patient’s coagulation status becomes increasingly important in preparation for major surgery with significant expected blood loss and a high likelihood of transfusion. This will also influence the intravenous access and invasive monitoring planned for the procedure.

If the patient is taking any form of NSAID, aspirin, antiplatelet therapy, or anticoagulation, it is important to be familiar with guidelines for reversal and discontinuation prior to surgery [Reference Nguyen, DasGupta, Wahed and Cruz1]. This will often require a multidisciplinary discussion involving the surgeon, anesthesiologists, and the patient’s primary care physician (often a cardiologist). Depending on the location and type of surgery, the surgical team may permit the patient to remain on some “blood-thinning” medications, if the risk of discontinuing these is greater than that of significant surgical bleeding (such as recent percutaneous coronary intervention (PCI) with stent placement, recent cerebrovascular accident (CVA), etc.).

Although typical preoperative laboratory values can be quite revealing, it remains crucial to perform pertinent parts of the physical examination when assessing the patient’s coagulation status. The patient may exhibit oozing at their mucosal surfaces, extensive ecchymosis, joint deformation, or jaundice indicating possible liver disease, or they may develop hematuria, with significant thrombocytopenia [Reference Nguyen, DasGupta, Wahed and Cruz1]. The patient may report a history of hematoma formation out of proportion to any trauma they have incurred. Perhaps the patient is a female who has given birth, and reports a history of significant blood product transfusion in the absence of obstetric complications.

Prior to major surgery, the patient will often undergo some form of preoperative medical workup, including a visit with their primary provider and laboratory tests, and often additional cardiac workup (ECG, transthoracic echocardiography (TTE), stress test) in patients with a history of cardiac disease or with cardiac risk factors. Standard blood work should include CBC, CMP, coagulation studies (prothrombin time (PT), activated partial thromboplastin time (aPTT), international normalised ratio (INR)). Collectively, these values can provide abundant information about the presence of coagulopathy, the likelihood of major bleeding, the risk of clotting, and the likelihood of transfusion. Also, blood bank testing should include T+S. If this screen is positive, it indicates the patient has antibodies present and more time is required for the blood bank to investigate the nature of the antibody and whether or not it is clinically significant [Reference Nguyen, DasGupta, Wahed and Cruz1].

Preoperative Management of Antiplatelets and Anticoagulants

Antiplatelet and anticoagulation medications are often prescribed for postprocedural management of vascular stents, coronary artery disease, or a primary coagulation disorder, and it is important to be familiar with their properties. When patients are scheduled for surgery, a review of their medication list should identify any drugs of this class. It is essential to understanding why the patient is prescribed the medication and whether or not these medications should be held prior to surgery [Reference Kitchens, Kessler, Konkle and Garcia2]. This decision may depend on the potential for significant blood loss, the condition for which the patient is prescribed the medication, emergent versus scheduled surgery, the type of surgery being performed, assessment of bleeding and thromboembolic risk, and the necessary duration of discontinuation, among other reasons.

In the event that anticoagulants or antiplatelet medications need to be discontinued, the patient should be educated on the proper time to stop the medication preoperatively. Multidisciplinary discussion may be warranted to decide when it is safe for the patient to resume their medication postoperatively. Medications such as warfarin require discontinuation well in advance (4–7 days prior), and it may be prudent to repeat coagulation labs to ensure the INR reflects adequate warfarin reversal prior to surgery (often target INR <1.5) [Reference Kitchens, Kessler, Konkle and Garcia2]. When holding warfarin, there is the option to “bridge” the patient to an anticoagulant with a shorter half-life, such as enoxaparin, so that the patient does not need to be without anticoagulation for as long a period of time. Many of the newer oral anticoagulants have a shorter half-life and therefore require less time to reverse. There are also antidotes for some of these medications, making them essentially immediately reversible. Heparin and low-molecular-weight heparin (LMWH) have relatively short half-lives and require discontinuation 4–6 hours, and 24 hours, prior to surgery, respectively [Reference Kitchens, Kessler, Konkle and Garcia2]. Reversal of heparin and LMWH can be monitored with partial thromboplastin time (PTT), and protamine is also available for immediate reversal if necessary.

Antiplatelet drugs include aspirin, P2Y12 inhibitors, and glycoprotein 2b/3a inhibitors. In order to monitor the reversal of these medications, platelet function testing with platelet aggregation studies is the most reliable and considered the gold standard. Many of these medications will also affect thromboelastography (TEG) values and require ample time for reversal, with even longer half-lives in patients with renal dysfunction. Although there is a large range of half-lives within this class of medications, abciximab requires the longest time for reversal and typically discontinuation 2 weeks prior to surgery [Reference Kitchens, Kessler, Konkle and Garcia2].

Direct thrombin inhibitors and direct Xa inhibitors comprise the last two major classes of anticoagulation. The most commonly used direct thrombin inhibitors are bivalirudin (intravenous) and dabigatran (oral), and the most common direct Xa inhibitors are rivaroxaban and apixaban (both administered orally). Direct thrombin inhibitors do not have specific antidotes but are removable by dialysis, and this method has been employed in patients who are actively bleeding. With advance notice, these medications require no more than a few days of discontinuation prior to surgery. Direct Xa inhibitors, on the other hand, are not removable by dialysis. Their reversal may be monitored with antiXa levels, and they too require a few days of discontinuation prior to surgery [Reference Nguyen, DasGupta, Wahed and Cruz1].

Laboratory Testing

Laboratory tests can provide information about individual components in the coagulation cascade. A CBC informs about the starting hematocrit and the need for red blood cell transfusion, whereas a platelet count informs about the need for platelet transfusion. PT can evaluate the extrinsic and common pathways of coagulation [Reference Nguyen, DasGupta, Wahed and Cruz1]. In this test, the patient’s plasma is mixed with thromboplastin and calcium, and a clotting time is determined. These values are standardized across institutions using the INR, to account for differing thromboplastins used. PT can be prolonged due to warfarin, vitamin K deficiency, inherited or acquired factor deficiencies, or inhibitors. The PTT measures the intrinsic and common pathways, including prothrombin and fibrinogen. The patient’s plasma is mixed with an activating agent such as silica, calcium, and phospholipid. The PTT can be prolonged due to heparin, factor deficiencies, inhibitors such as factors VIII and IX, anticoagulant or lupus antibody, and vWD [Reference Kitchens, Kessler, Konkle and Garcia2].

These standard laboratory tests are limited in their ability to guide the decision to transfuse blood products such as fresh frozen plasma (FFP), platelets, and cryoprecipitate, because they do not reliably predict a patient’s risk of bleeding. Viscoelastic testing, invented in 1948, analyzes a developing clot from whole blood. Real-time results can be used to treat specific deficits in the clotting cascade of a patient. Why do conventional coagulation tests (CCTs) fail to capture this picture? The PT/INR is measured from plasma and correlates poorly with clotting time. Plasma lacks certain activators, as well as the presence of pro- and anticoagulants present in whole blood. Tissue factor expressed on cells such as monocytes also affects actual clotting and will not be a component of PT/INR. The strength of the clot is determined by platelets and fibrinogen. Due to this tight interplay, the direct platelet count is not a reliable measure of a patient’s ability or tendency to clot and whether the clot will be strong. Viscoelastic testing such as TEG and rotational thromboelastometry (ROTEM) can provide a global picture of coagulation and fibrinolysis over time, thereby providing valuable and evidence-based guidance for therapy [Reference Mallett5, Reference Mackman, Tilley and Key6].