This is frequently encountered in preoperative gynecologic surgery evaluation. In the absence of a clear etiology, evaluation serves to potentially correct reversible causes. Queries focus on signs of symptomatic anemia such as fatigue, dyspnea with exertion, and palpitations. Inquiry also seeks to identify risk factors for underlying cardiovascular disease as anemia is less well tolerated in these individuals. The physical examination incorporates thorough pelvic and rectal examination, stool guaiac screening, and urinalysis.
With chronic anemia, erythrocyte indices derived from a CBC reflect a microcytic, hypochromic anemia and show decreases is mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC). Moreover, in classic iron-deficiency anemia from chronic blood loss, an elevated platelet count and decreased reticulocyte count can be seen. In those for whom the cause of anemia is unclear, those with profound anemia, or those who fail to improve with oral iron therapy, addition testing is prudent. Iron studies, vitamin B12, and folate levels are often indicated. Iron-deficiency anemia produces low serum ferritin and iron levels, elevated total iron-binding capacity, and normal vitamin B12 and folate levels.
Several pharmacologic options are available for preoperative iron supplementation. For oral intake, ferrous sulfate (Feosol, Slow Fe), ferrous gluconate (Fergon), ferrous fumarate (Ircon, Fero-Sequels), and iron polysaccharide (Ferrex) are available. Importantly, each of the ferrous salts has a different content of elemental iron. In general, therapy to correct iron deficiency ideally provides 150 to 200 mg of elemental iron daily. Thus, common and equivalent oral replacement regimens include ferrous sulfate, 325 mg tablet (contains 65 mg elemental iron), or ferrous fumarate, 200 mg tablet (contains 64 mg elemental iron), three times daily. Okuyama and associates (2005) found that provision of 200 mg of elemental iron 2 weeks preoperatively significantly reduced the need for intraoperative transfusion. Constipation is the primary source of preparation intolerance and can be improved with dietary changes, bulk laxatives, and stool softeners (Table 25-6).
In addition to oral forms, several Food and Drug Administration (FDA)-approved intravenous (IV) iron preparations are currently available. These include ferric gluconate (Ferrlecit), iron sucrose (Venofer), ferumoxytol (Feraheme), ferric carboxymaltose (Injectafer), and low-molecular-weight iron dextran (INFeD) (DeLoughery, 2014). The newer preparations have a much lower risk of anaphylactic reactions and are considered safe (Shander, 2010). The hemoglobin effects can be seen as quickly as 1 week after the first dose. For most women, iron therapy administered orally is effective to correct anemia. However, these IV forms may be most appropriate for women with poor absorption secondary to gastrointestinal disease, those with chronic renal disease, or those with an intolerance or lack of response to oral iron.
In women with acute bleeding, transfusion may be required perioperatively. The decision to transfuse depends in part on a patient’s cardiac status. A full discussion of resuscitation is found in Chapter 40.
Autologous Blood Donation
Fear of infection from allogeneic blood transfusions has led to development of autologous transfusion practices. Two of the most popular options include preoperative autologous donation and salvage autologous transfusions. Both are discussed in detail in Chapter 40 (Vanderlinde, 2002).
Coagulopathies are generally grouped into two categories—inherited or acquired. Of acquired forms, a careful review of systems and complete medication list, including herbal preparations, may highlight potential causes. In either form, disorders involving platelets or clotting factors can be identified with a careful history and physical examination. A personal history of easy bruising, unexpected amounts of bleeding with minor injury, or lifelong menorrhagia alert a clinician to the possibility of coagulopathy. Screening for coagulopathies is outlined in Chapter 8, and the specifics of replacement are described in Chapter 40. In general, for those undergoing procedures, a transfusion threshold of ≤50,000/μL is used, and for major surgery, ≤100,000/μL (James, 2011).
In patients who take anticoagulants following a venous thromboembolism (VTE), the timing of surgery can often lower the risk of postoperative VTE. After an acute VTE, the recurrence risk without anticoagulation is between 40 and 50 percent. However, the risk of recurrent disease drops significantly after 3 months of warfarin therapy. Moreover, a delay in surgery and continued warfarin therapy for an additional 2 to 3 months (6 months total) drops the recurrence risk to 5 to 10 percent and avoids a need for preoperative heparin (Kearon, 1997; Levine, 1995). Thus, in those with recent VTE, a surgical delay, if feasible, may be advantageous and should be considered. When surgery must proceed, protocols for anticoagulant management are described next.
Women with atrial fibrillation, mechanical heart valve, or recent VTE are at increased risk for VTE. As a result, chronic oral warfarin therapy is typically prescribed. For these patients, a surgeon must compromise between the need for anticoagulation and risk of surgical bleeding complications. The American College of Obstetricians and Gynecologists (2014b) has summarized recommendations to address this balance (Table 39-2). In general, anticoagulation is typically halted prior to surgery and started shortly postoperatively. Unfortunately, the effects of warfarin reverse slowly. Thus, patients are often transitioned or “bridged” to heparin, which can be stopped and restarting more readily. Both low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH) are options (Table 39-3). Of LWMH choices, enoxaparin (Lovenox) is commonly selected. During bridging, warfarin is stopped several days before surgery, and heparin is begun (Douketis, 2012; White, 1995). In those with a therapeutic INR (between 2.0 and 3.0), approximately 5 to 6 days are required for this ratio to reach 1.5. Once this is achieved, surgery can safely proceed. During bridging therapy, the last dose of LMWH is administered 24 hours prior to surgery. With UFH, therapy is halted 4 to 6 hours prior to surgery (Douketis, 2012).
TABLE 39-2Perioperative Management of Patients on Chronic Antithrombotic Therapy ||Download (.pdf) TABLE 39-2 Perioperative Management of Patients on Chronic Antithrombotic Therapy
|Condition ||Bleeding Risk ||High VTE Risk ||Moderate VTE Risk ||Low VTE Risk |
|Prior VTE ||High ||Protocol A ||Protocol C ||Protocol C |
| ||Moderate ||Protocol A ||Protocol B or C |
Consider mechanical prophylaxis
|Protocol C |
|Atrial fibrillation ||High ||Protocol A ||Protocol C or B ||Protocol C or B |
| ||Moderate ||Protocol A ||Protocol A or B ||Protocol B or C |
|Mechanical heart valve ||High ||Protocol A ||Protocol A or B ||Protocol C |
| ||Moderate ||Protocol A ||Protocol A ||Protocol C or B |
|Protocol A: Use bridging therapy with therapeutic-dose low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH). Therapeutic-dose enoxaparin is 1 mg/kg subcutaneously (SC) twice daily or 1.5 mg/kg once daily. Therapeutic-dose intravenous (IV) UFH is 80 units/kg IV push, then 18 units/kg/hr. |
Protocol B: Use bridging therapy with low-dose LMWH or low-dose UFH. Low-dose enoxaparin is 30 mg twice SC daily or 40 mg once SC daily. Low-dose UFH is 5000–7500 units SC twice daily.
Protocol C: Stop long-term anticoagulation therapy. Do not use bridging therapy. Restart long-term anticoagulation after surgery. Use mechanical prophylaxis with an intermittent compression device during surgery and until long-term anticoagulation is therapeutic.
TABLE 39-3Anticoagulant Management ||Download (.pdf) TABLE 39-3 Anticoagulant Management
|Bridging protocol for warfarin |
|5 days before surgery ||Stop warfarin; start LMWH or UFH |
Stop LMWH 24 hours before surgery or stop UFH at least 4–6 hours before surgery
|1 day before surgery ||Check INR. If INR >1.5, give 1–2 mg of oral vitamin K |
|Surgery day ||Start LMWH or UFH 12–24 hours after surgery, if bleeding risk is low |
|1 day after surgery ||Start warfarin |
|5 days after surgery ||Stop LMWH or UFH once INR is >2. Continue warfarin |
| Protocol for direct oral anticoagulant |
|1–2 days before surgery |
1 day after surgery
|Stop agent: dabigatran 2 days prior; apixaban and rivaroxaban 1 day prior |
| Protocol for antiplatelet agents |
|7 days before surgery |
1 day after surgery
|Stop aspirin or clopidogrel |
Start agent 12–24 hours after surgery
Unfortunately, emergency surgery may not allow time for such bridging. In these cases, warfarin is halted, and vitamin K is provided. This vitamin promotes factor synthesis, and in urgent cases, a 5- to 10-mg IV dose is suitable (Holbrook, 2012). To minimize the anaphylactic risk, vitamin K is mixed in a minimum 50 mL of IV fluid and administered over at least 20 minutes. Vitamin K requires 4 to 6 hours to achieve clinical effects. Thus, fresh frozen plasma (FFP) may be added at a dose of 15 mL/kg, and each FFP unit has a volume of 200 to 250 mL. Prothrombin complex concentrate (PCC) is a human-derived product containing factors II, IX, and X. PCC does not require thawing and may be used in place of FFP (Ageno, 2012).
Although warfarin antagonizes all vitamin K-dependent clotting factors, newer direct oral anticoagulants (DOACs) inhibit specific factors. The three currently licensed medications are dabigatran (Pradaxa), which targets factor IIa (thrombin), and rivaroxaban (Xarelto) and apixaban (Eliquis), which target factor Xa. Because of their recent introduction, few studies provide recommendations for their perioperative management (Kozek-Langenecker, 2014). The pharmacologic half-life is 14 hours for dabigatran and 9 hours for rivaroxaban and apixaban (Schaden, 2010). Thus, in women with normal preoperative creatinine clearance, stopping rivaroxaban and apixaban 24 hours prior to surgery and halting dabigatran 48 hours prior to surgery is reasonable. The withdrawal time is doubled if the creatinine clearance is <50 mL/min or the risk of perioperative bleeding is high (Ortel, 2012).
For the DOACs, global coagulation tests such as INR, PT, and activated partial thromboplastin time (aPTT) less reliably reflect coagulant activity. For the factor Xa inhibitors rivaroxaban and apixaban, anti-factor Xa assays can be used to measure their activity. For dabigatran, an aPTT >90 seconds and an INR >2 suggest possible overdosing (Lindahl, 2011). Also for dabigatran, thrombin time testing is more sensitive and normal values exclude significant anticoagulant effect. However, the turnaround time with this specific test can be long.
For emergent surgery, the DOACs have no antidote, and management of life-threatening bleeding remains empirical. Fortunately, anticoagulant effects rapidly dissipate because of the drugs’ short half-lives. Indirect evidence suggests that recombinant factor VIIa (NovoSeven) or a prothrombin complex concentrate may be helpful (Ageno, 2012).
Last, antiplatelet agents such as aspirin and clopidogrel (Plavix) may increase surgical bleeding. These are generally stopped 7 days prior to surgery (American College of Obstetricians and Gynecologists, 2014b).
After surgery, heparin, either UFH or LMWH, is restarted 12 to 24 hours after major surgery (see Table 39-3). Oral warfarin therapy is started concurrently as several days are required to regain therapeutic levels (Harrison, 1997; White, 1994). Once the INR ranges between 2 and 3, then heparin is discontinued. DOACs are typically restarted 24 hours following surgery. Antiplatelet agents may be resumed 12 to 24 hours following surgery. In all cases, agents are begun only after surgical hemostasis is confirmed.