Perioperative Management of Patients Who Are Receiving Oral Anticoagulant Therapy

Introduction

The perioperative management of patients who require interruption of a vitamin K antagonist (VKA) because of surgery or another non-invasive procedure is a common and sometimes challenging clinical problem. Bridging anticoagulation refers to the use of a short-acting anticoagulant,which is usually therapeutic-dose subcutaneous low-molecular-weight heparin (LMWH) such as enoxaparin 1 mg/kg twice-daily, administered during the time when a VKA is interrupted and there is no therapeutic anticoagulation. However, there is no standardized definition of ’bridging anticoagulation’ and other treatment regimens, including low-dose (enoxaparin 40 mg once-daily) or intermediate-dose (eg, enoxaparin 40 mg twice-daily) LMWH regimens, have been used, particularly in selected patients at high risk for bleeding complications.

Although perioperative anticoagulant management may be straightforward in many cases, requiring simple interruption and postoperative resumption of VKA therapy, there are also many instances where management decisions may affect clinical outcomes, whether thromboembolic or bleeding. In all cases management decisions are anchored on weighing perioperative risks for thromboembolism and bleeding.

The objectives of this chapter are: 1) to stratify patients according to their risk for arterial or venous thromboembolism if VKA therapy is stopped and the risk for bleeding associated with surgery or procedure; 2) to provide a practical approach to the perioperative interruption and resumption of VKA therapy; 3) to provide a practical protocol for the administration of bridging anticoagulation when required.

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Case 61-1

A 54-year-old woman with rheumatic valvular heart disease requires hysterectomy (uterine fibroids). She has a St. Jude mechanical prosthetic valve in the mitral position and she is on warfarin. The perioperative management of anticoagulant therapy should start with the assessment of her thromboembolic risk, which should be considered high in the presence of any mitral valve prosthesis.

The second step is represented by the assessment of bleeding risk, which can be considered nonhigh because the type and location of surgery do not involve critical sites or major tissue injury or highly vascularized organ.

A preoperative bridging regimen is suggested here:

Day –5: stop warfarin (may stop on day –6 if INR range is 2.5 –3.5)
Day –3: start therapeutic-dose heparin (SC LMWH or IV UFH)
Day –1:
- check INR if possible (if INR > 1.5, vitamin K 1 –2 mg orally can be administered)
- if SC LMWH was chosen, give the last dose in the morning (this dose must be reduced by 50% in case of once-daily dosing regimen)
- if IV UFH was chosen, stop infusion 4 hours before surgery

A post-operative bridging regimen is suggested here:

Day 0: after assessing surgical site hemostasis, warfarin can be resumed on the evening after surgery, if feasible
Day +1 to +3: resume therapeutic-dose LMWH or UFH when hemostasis is secure, and in no case before 12 hours after surgery (typically on the morning afterwards)
Day +5 to +6: stop LMWH or UFH when INR is therapeutic

A cautionary note: there are no randomized controlled trials that definitively guide the clinician regarding which patients must receive bridging therapy to avoid devastating thromboembolic complications and which patients should not due to increased risk of perioperative bleeding associated with bridging. Although most practitioners use the CHADS scoring system, clinical judgment is still required for each patient at the bedside. For patients with additional comorbidity that increases the risk of bleeding such as new renal failure, thrombocytopenia, or an elevated INR prior to warfarin administration, it is important to define the additional risk of increased bleeding and weigh that against the known risk of thromboembolic complications. Significant renal failure, thrombocytopenia, or elevated INR requires further investigation and treatment, usually prior to any initiation of anticoagulation.

Perioperative Thromboembolic and Bleeding Risk Stratification Thromboembolic Risk Stratification

Thromboembolic Risk Stratification

Patients who are receiving oral anticoagulant therapy, usually with warfarin, represent a spectrum of thromboembolic risk that is determined primarily by the clinical indication for warfarin therapy and secondarily, individual patient characteristics. The most frequent clinical indications for warfarin therapy are chronic atrial fibrillation (AF), mechanical heart valves (MHV), and venous thromboembolism (VTE). The principal thromboembolic risk is arterial in patients with atrial fibrillation or a mechanical heart valve, and venous in patients with prior VTE. When considering this risk, both the risk of such events and their clinical consequences should be considered. Although there are no validated risk stratification schemes to quantify thromboembolic risk, a suggested risk classification scheme separating patients into high, moderate, or low risk categories for thromboembolism is outlined below and in Table 61-1, 61-2, 61-3

Table 61-1 Stoke Risk in Atrial Fibrillation: CHADS2 Score

Risk Criteria	Score
Congestive heart failure	1
Hypertension	1
Age ≥ 75 years	1
Diabetes	1
Prior Stroke or transient ischemic attack	2

Table 61-2 Stroke Risk According to CHADS2 Score in Patients with Nonvalvular AF Not Treated with Warfarin

CHADS2 Score	Annual Stroke Rate (95% Confidence Interval)
0	1.9 (1.2–3.0)
1	2.8 (2.0–3.8)
2	4.0 (3.1–5.1)
3	5.9 (4.6–7.3)
4	8.5 (6.3–11.1)
5	12.5 (8.2–17.5)
6	18.2 (10.5–27.4)

Table 61-3 Suggested Risk Stratification Scheme for Perioperrative Arterial and Venous Thrombembolism

	Indication for WARFARIN therapy
Thrombotic Risk	Atrial fibrillation	Mechanical Heart Valves	VTE
High	CHADS2 score: 5 or 6 Recent (<3 months) stroke or TIA Rheumatic valvular heart disease	Any mechanical mitral valve prosthesis Older aortic mechanical valve prosthesis (caged-ball, tilting disk) Recent (<6 months) stroke or TIA	Recent (<3 months) VTE Severe thrombophilia†
Moderate	CHADS2 score: 3 or 4	Bileaflet aortic valve prosthesis with at least 1 risk factor*	VTE within 3–12 months Nonsevere thrombophilia§ Recurrent VTE Active cancer
Low	CHADS2 score: 0–2 (without prior stroke or TIA)	Bileaflet aortic bileaftlet without any risk factors*	VTE > 12 months

High Risk for Thromboembolism (>10% Per Year):

AF: CHADS2 score of 5 or 6; recent (within 3 months) stroke or transient ischemic attack (TIA); rheumatic valvular heart disease
MHV: mitral valve prosthesis; older generation (caged-ball or tilting disk) aortic valve prosthesis; recent (within 3 months) stroke or TIA
VTE: prior VTE within past 3 months; severe thrombophilia (protein C, protein S, or antithrombin deficiency, antiphospholipid syndrome, combined thrombophilic abnormalities)

Moderate Risk for Thromboembolism (5–10% Per Year):

AF: CHADS2 score of 3 or 4
MHV: aortic bileaflet valve prosthesis and 1 of the following: atrial fibrillation, prior stroke or TIA, other stroke risk factors (heart failure, hypertension, age ≥75 years, diabetes)
VTE: prior VTE within past 3 and 12 months; nonsevere thrombophilia (heterozygous factor V Leiden or prothrombin mutation); recurrent VTE; active cancer (treated within 6 months or palliative)

Low Risk for Thromboembolism (<5% Per Year):

AF: CHADS2 score of 0 to 2, without previous stroke or transient ischemic attack
MHV: aortic bileaflet valve prosthesis without atrial fibrillation or any other stroke risk factors
VTE: prior VTE more than 12 months before and no other risk factors (among above-mentioned)

In addition to this classification, which aims to quantify thromboembolic risk, the qualitative or clinical impact of an event should be considered. Thus, the impact ofthe arterial thromboembolic event, especially stroke, islikely to be greater than that of a recurrent venous event.

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Practice Point

Thromboembolic risk stratification should take into account:

The risk of thromboembolism:
- High > 10% per year
- Moderate 5–10% per year
- Low < 5% per year
The clinical impact of an event (with arterial embolism likely greater than recurrent venous thrombosis):
- Embolic stroke can result in death or major disability inabout 70% of patients.
- Thrombosis of a mechanical heart valve is fatal in about 15% of patients.
- Recurrent VTE is fatal in 4% to 9% of patients.

Bleeding Risk Stratification

The risk for perioperative bleeding is determined primarily by the type of surgery that is planned and secondarily on patient-specific characteristics. In terms of surgical factors that determine risk for bleeding, these include the extent of surgery and associated tissue injury, the anatomical region involved, and whether hemostasis is actively attained, through suturing and cautery, or left to occur by secondary intent. The risk for bleeding should not only consider the anticipated amount of blood loss but also the clinical consequences of bleeding.

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