Page 2594 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 159 Hematologic Problems in the Surgical Patient 2311

completed, but questions about optimal dosing, cost-effectiveness, TABLE Perioperative Management Strategies for Patients on
and safety remain to be fully answered. Furthermore, it is still question- 159.3 Chronic Oral Anticoagulant Therapy
able whether rFVIIa should be used prophylactically in liver transplan-
tation patients outside of a prospective clinical trial. 140 Clinical Situation Suggested Anticoagulation Management
Low bleeding-risk surgery • Consider reducing dose of warfarin
(dental, cataract, skin) to achieve INR ≤2.0
PERIOPERATIVE ANTICOAGULATION MANAGEMENT • Consider holding dose of DOAC until
after the procedure
Hematologists are frequently consulted for advice on the periopera-
tive management of patients who are taking oral anticoagulants. Low thrombotic risk • Stop warfarin 4–5 days prior to
Important considerations to be taken into account include: (1) the Aortic valve prosthesis surgery, safe to operate when INR
bleeding risk associated with the surgery; (2) the underlying indica- without other thrombotic ≤1.5
a
tion for anticoagulant therapy; (3) in the case of secondary anti- risk factors • Hold DOACs for 5 half-lives
thrombotic prophylaxis, the remoteness of the most recent thrombotic or – dabigatran for 3–4 days,
event; (4) other comorbid conditions that may increase the risk for AF with low stroke risk rivaroxaban, apixaban, edoxaban for
thrombosis and/or the potential consequences of thrombosis while or 2–3 days
oral anticoagulation is temporarily interrupted; and (5) the half-life VTE >3 months previously • Restart warfarin in evening of the
of the anticoagulant agent. Regarding the first point, experience has day of surgery after hemostasis
accumulated in recent years suggesting that many relatively minor secured; restart DOACs on
procedures can be carried out without any interruption of warfarin postoperative day 3 or 4
141
or direct oral anticoagulant (DOAC) therapy. These include minor • Start prophylactic LMWH on the
dental procedures (single or multiple extraction, endodontic proce- morning of the day after surgery and
dure), cataract removal, minor dermatologic procedures, and low-risk continue until INR >1.8 or full dose
endoscopy procedures. Audits have suggested that discontinuation of of DOACs resumed
anticoagulation is excessively frequent in these situations and discor- Moderate thrombotic risk • Stop VKA 5 days before surgery
142
dant with guidelines. Apart from the risk for thromboembolism, Mitral or multiple valve • Begin twice-daily LMWH in
the inappropriate use of bridging therapy also places patient at risk prostheses therapeutic doses starting 3 days
for bleeding complications. Suggested management strategies are or before surgery with last dose at least
summarized in Table 159.3. Aortic prosthesis with risk 12 h prior to surgery
Traditionally, patients on chronic oral anticoagulation with warfa- factors for thrombosis • Hold DOACs for 5 half-lives
rin were admitted to hospital several days before surgery for “bridg- or – dabigatran for 3–4 days,
ing” anticoagulation, at which time warfarin was discontinued and AF at high stroke risk rivaroxaban, apixaban, edoxaban for
dose-adjusted unfractionated heparin (UFH) was administered by or 2–3 days; no bridging
continuous infusion. The short half-life of UFH allows it to be safely VTE within past 3 months • Restart warfarin in evening of the
discontinued approximately 4–6 hours ahead of the procedure. This day of surgery after hemostasis
was followed by the use of LMWH in place of UFH. 143-145 LMWH secured; restart DOACs on
has the advantage that in most patients with normal renal function, postoperative day 3 or 4
no monitoring is required, so that therapy can be administered in the • Start prophylactic LMWH on the
outpatient setting. In addition, the risk for heparin-induced throm- morning of the day after surgery and
146
bocytopenia is less with LMWHs. However, the longer half-life continue until INR >1.8 or full dose
(generally in the range of 4–6 hours) necessitates withdrawal of these of DOACs resumed
agents at least 12 hours (for prophylactic doses) or 24 hours (for a Risk factors include caged-ball or single tilting-disk valve, AF, history of stroke/
full therapeutic doses) preoperatively, although even then significant transient ischemic attack/other embolic event, left ventricular failure, underlying
147
circulating anticoagulant activity may remain in the plasma. A hypercoagulable state, including cancer.
recent randomized trial suggests that bridging with LMWH does AF, Atrial fibrillation; DOAC, direct oral anticoagulant; INR, international
normalized ratio; LMWH, low-molecular-weight heparin; VKA, vitamin K
not reduce the risk of thromboembolic events and increases the antagonist (i.e., warfarin); VTE, venous thromboembolism.
148
risk of bleeding in patients with atrial fibrillation. Although these
results have changed practice, it is important to note that atrial
fibrillation patients with prior stroke were underrepresented in
the study. concentrate (PCC; 25–50 units/kg) is preferred over plasma to
Temporary interruption of warfarin is often required for more control hemorrhage in warfarin-treated patients with active bleed-
major surgery. Even with a normal diet, 4–5 days should be allowed ing. 150,152 These concentrates are manufactured by fractionation of
for full or near-full reversal of warfarin when it is being targeted to pooled plasma and contain the vitamin K–dependent factors II, VII,
an INR of 2.0–3.0. A more rapid reversal over 24–36 hours can be IX, and X. However, it is important to be aware that there is signifi-
achieved if necessary by administration of a small oral dose of vitamin cant heterogeneity among these agents, with some (three-factor PCC)
K1 (1.0–2.5 mg). 149,150 Large doses of vitamin K1 (>10 mg) are having a low concentration of factor VII, which may leave the INR
generally unnecessary for this purpose and will lead to prolonged prolonged following administration. 153
refractoriness to warfarin after it is reinitiated. Although frequently In recent years, DOACs, oral anticoagulants that directly inhibit
used, subcutaneous administration of vitamin K1 is associated with thrombin or factor Xa, have been licensed for the prevention of stroke
highly variable absorption and should be avoided. Intravenous and systemic embolism in patients with atrial fibrillation and for
vitamin K1 has the advantage of more rapid INR reversal compared prevention and treatment of VTE (see Chapter 149). A working
151
with the oral route, but it should be administered slowly to avoid knowledge of the respective elimination half-lives of these agents is
anaphylactoid reactions. Urgent reversal of oral anticoagulation important in deciding when and if to discontinue before elective
before surgery may call for the administration of fresh-frozen plasma, procedures. In addition, an appreciation of the dominant mechanism(s)
although large volumes (15–20 mL/kg) are usually required to reverse of clearance that may affect the elimination half-life is essential (Table
the INR, and indeed complete normalization cannot usually be 159.4). In general, when the procedure is considered to be more than
achieved. Furthermore, the effect is relatively short-lived because of minor, and the aim is to have negligible amounts of drug (<10%) in
the short half-life (approximately 6 hours) of transfused factor VII. the circulation at the time of surgery, the drug should be discontinued
Therefore concomitant vitamin K1 administration is required to at a time before surgery equivalent to four to five half-lives. This
ensure maintenance of adequate hemostasis. Prothrombin complex would imply 2–3 days (48–60 hours) for dabigatran and 1–2 days