Perioperative Management of Antiphospholipid ... - Springer Link

Curr Rheumatol Rep (2014) 16:426 DOI 10.1007/s11926-014-0426-7

SURGERY AND PERIOPERATIVE CARE (CR MACKENZIE AND SM GOODMAN, SECTION EDITORS)

Perioperative Management of Antiphospholipid Antibody-Positive Patients Katherine H. Saunders & Doruk Erkan & Michael D. Lockshin

Published online: 15 May 2014 # Springer Science+Business Media New York 2014

Abstract Perioperative management of antiphospholipid antibody (aPL)-positive patients is challenging because there are limited data on which to base recommendations. This population of patients is at high risk of thrombosis at the time of surgery; it is essential that medical and surgical teams devise a plan to minimize the patient’s risk of thrombosis without increasing bleeding risk. During the perioperative period, pharmacological methods should be combined with physical methods, patients should be closely observed for thrombosis, and any deviation from the normal course should be considered a potential aPL-related event. Periods without anticoagulation should be kept to an absolute minimum for aPL-positive patients with a history of thrombosis and physicians should keep in mind that thrombosis can occur despite optimum prophylaxis. Keywords Perioperative management . Antiphospholipid syndrome . Antiphospholipid antibodies . Surgery

Introduction Antiphospholipid syndrome (APS) is diagnosed in patients with vascular thrombosis and/or pregnancy morbidity in the

This article is part of the Topical Collection on Surgery and Perioperative Care K. H. Saunders Department of Medicine, New York-Presbyterian Hospital, 525 East 68th Street, Box 130, New York, NY 10065, USA e-mail: [email protected] D. Erkan (*) : M. D. Lockshin Barbara Volcker Center for Women and Rheumatic Diseases, Hospital for Special Surgery, Weill Medical College of Cornell University, 535 East 70th Street, New York, NY 10021, USA e-mail: [email protected] M. D. Lockshin e-mail: [email protected]

setting of persistently positive antiphospholipid antibodies (aPL) (Table 1) [1]. The tests most commonly used to detect aPL are lupus anticoagulant (LA) functional coagulation assay, anticardiolipin antibody (aCL) enzyme-linked immunosorbent assay (ELISA), and anti-β2-glycoprotein-I (aβ2GPI) ELISA. Diagnosis requires at least one clinical criterion and one laboratory criterion no less than twelve weeks but no more than five years apart. Antiphospholipid syndrome occurs both in patients with systemic autoimmune diseases, especially systemic lupus erythematosus (SLE), and in otherwise healthy people without underlying autoimmune disease (primary APS). Deep vein thrombosis (DVT) is the most common venous manifestation of APS and cerebrovascular accident (CVA) is the most common arterial manifestation. Livedo reticularis, thrombocytopenia, nephropathy, and cognitive dysfunction are some of the “non-criteria” manifestations of APS. Catastrophic APS (CAPS) is a rare, rapidly progressive, life-threatening form of APS that is generally associated with small vessel involvement and causes multiple organ thromboses [3]. aPL, usually in low titer, are found in approximately 30– 40 % of SLE patients, 20 % of women with recurrent fetal loss, and up to 10 % of the general population; persistent LA test positivity and high titer aCL/aβ2GPI positivity are relatively uncommon, however [4, 5]. Cross-sectional and prospective cohort studies reveal that “aPL-positivity” predicts future vascular events; however, there is no well-established one-to-one association between aPL and thrombosis in humans. Furthermore, the number of general population studies designed on the basis of different aPL thrombosis risk profiles is limited. The “second-hit hypothesis” proposes that aPLpositive patients require an initiating event, for example a surgical procedure, to develop thrombosis [6, 7]. This hypothesis is supported by studies illustrating that the risk of vascular events in aPL-positive patients increases with increasing number of thrombosis risk factors, for example genetic clotting disorders, cardiovascular disease risk factors, oral contraceptives, pregnancy, and venous catheters. At least 50 % of APS

426, Page 2 of 8 Table 1 Revised Sapporo Classification Criteria for the Antiphospholipid Syndrome (modified from refs. [1, 2••]) Clinical criteria 1. Vascular thrombosis: • One or more clinical episodes of arterial, venous, or small vessel thrombosis, in any tissue or organ. 2. Pregnancy morbidity: • One or more unexplained deaths of a morphologically normal fetus at or beyond the 10th week of gestation, or • One or more premature births of a morphologically normal neonate before the 34th week of gestation because of: eclampsia, severe preeclampsia, or recognized features of placental insufficiency, or • Three or more unexplained consecutive spontaneous abortions before the 10th week of gestation, with maternal anatomic or hormonal abnormalities and paternal and maternal chromosomal causes excluded. Laboratory criteria 1. Lupus anticoagulant present in plasma, on two or more occasions at least 12 weeks apart, detected according to the guidelines of the International Society on Thrombosis and Hemostasis, and/or 2. Anticardiolipin antibody of IgG and/or IgM isotype in serum or plasma, present in medium or high titer (i.e. >40 GPL or MPL, or greater than the 99th percentile), on two or more occasions, at least 12 weeks apart, measured by a standardized enzyme-linked immunosorbent assay (ELISA), and/or 3. Anti-β2-glycoprotein-I antibody of IgG and/or IgM isotype in serum or plasma (titer greater than the 99th percentile) present on two or more occasions, at least 12 weeks apart, measured by a standardized ELISA. Definite APS is present if at least one of the clinical criteria and one of the laboratory criteria are met. Classification of APS should be avoided if less than 12 weeks or more than 5 years separate the positive aPL test and the clinical manifestation.

patients have a reversible risk factor at the time of thrombosis; in two cross-sectional studies we demonstrated that 6–18 % of APS patients had undergone a surgical procedure at the time of their thrombotic event [8, 9]. Furthermore, over 50 % of CAPS episodes are initiated by, for example, infection (35 %), trauma, or invasive procedures (13 % combined) [10]. Because thrombosis is multifactorial, risk stratification and prevention strategies should consider traditional cardiovascular and venous thrombosis risk factors, other comorbidities, systemic autoimmune diseases, and the aPL profile during preoperative assessment of thrombotic risk. Reversible risk factors should be identified and eliminated. When surgery or other high-risk situations are unavoidable, aggressive prophylaxis is crucial. The purpose of this article is to summarize the perioperative management strategies for aPL-positive patients undergoing non-cardiac surgery. A detailed discussion of aPLspecific perioperative strategies for non-cardiac and cardiac surgery can be found elsewhere [2••, 11••].

Preoperative Planning and Communication Given the high risk, elective surgery should be strongly discouraged and the least invasive option should be pursued.

Curr Rheumatol Rep (2014) 16:426

When surgery is elective, the patient should participate in the creation of a thrombosis prophylaxis plan and he/she should be familiar with all aspects of medical and physical thrombosis prevention, including early mobilization after surgery. Communication between the medical, surgical, and anesthesiology teams is essential for a successful outcome. A multidisciplinary meeting or at least verbal communication among the teams is important. All participants must agree on anticoagulant doses as well as timing of initiation and discontinuation of medications. Management strategies for potential perioperative complications should also be discussed.

Preoperative Patient Assessment A personalized management plan must take into account the patient’s comorbidities, aPL profile, aPL-associated thrombosis risk, and bleeding risk. Comorbidities, e.g., cardiac, pulmonary, hematologic, might increase the patient’s risk of thrombosis or complicate the management strategy. Antiphospholipid Antibody Profile A positive aPL test is not always clinically significant; transient aPL positivity is not uncommon, especially during infections [12]. Documentation of aPL persistence is therefore important. High titers of aCL, aβ2GPI ELISA, and IgG/M isotypes are more concerning than are lower titers and IgA isotypes. Whereas a positive LA test is a better predictor of thrombosis than aCL and aβ2GPI ELISA, false-positive and false-negative LA tests can occur for patients on anticoagulation [13, 14]. Documentation of a positive LA test requires four criteria according to International Society of Thrombosis and Haemostasis guidelines: 1. prolonged phospholipid-dependent coagulation screening test, for example activated partial thromboplastin time (aPTT) or dilute Russell viper venom time (dRVVT); 2. demonstration of an inhibitor by failure to correct a prolonged screening test in a mixing study (in which the patient’s plasma is combined with normal plasma); 3. phospholipid dependency demonstrated by shortening/ correction of a prolonged screening test on addition of excess phospholipid; and 4. exclusion of other inhibitors [15]. To classify an aPL profile as “clinically significant,” we recommend LA test positivity in accordance with the above guidelines, aCL IgG/M≥40 U, and/or aβ2GPI IgG/M≥40 U tested twice at least 12 weeks apart. Clinical judgment is required to determine thrombosis risk when aPL results are


equivocal, e.g., LA test not measurable because the patient is anticoagulated, aCL or aβ2GPI IgG/M titers between 20 and 39 U, and/or aCL or aβ2GPI IgA as the only positive aPL test. Thrombosis Risk Antiphospholipid antibody-positive patients can be considered in a range from asymptomatic aPL positivity for normal persons (no history of vascular events or pregnancy) to CAPS. As a general rule, all patients with a “clinically significant” aPL profile are at high risk for perioperative thrombosis. Although there are no comparative studies, patients with a history of CAPS are believed to be at highest risk, followed by aPL-positive patients with a history of arterial and/or venous thrombosis. In addition to aPL profile and history of aPL complications, other comorbidities that increase the risk of arterial and venous thrombosis should be assessed as potential contributors to a patient’s risk of thrombosis. Bleeding Risk Not only are aPL-positive patients at risk of bleeding from excessive anticoagulation, they are also sometimes susceptible to bleeding secondary to their underlying condition. Approximately 20 % of patients with APS develop thrombocytopenia. The mechanism has not been proved, but there is some evidence that aPL bind to platelet membranes and cause platelet destruction [16, 17]. Platelet counts are usually only mildly reduced (>70,000 platelets per microliter) and episodes of thrombocytopenia are rarely associated with major bleeding requiring treatment. Unfortunately thrombocytopenia does not protect aPL-positive patients against thrombosis. Increased aPTT or dRVVT reflects lupus anticoagulant; it is a thrombosis, not a hemorrhage, risk and cannot be corrected. Prothrombin time (PT) prolongation means the patient may have an antibody to prothrombin (factor II). Prolonged aPTT and minimally prolonged PT attributed to aPL are not contraindications for surgery; marked PT prolongation (internal normalized ratio [INR]>2.0) should prompt further evaluation before the procedure if possible. Prolongation of aPTT can also be because of von Willebrand disease and deficiency of, or an inhibitor to, any clotting factor besides factor VII. Prolonged PT can be secondary to many conditions including vitamin K deficiency, chronic liver disease, and deficiency or inhibition of factors II, V, VII, and X. Oral medications, for example oral direct thrombin and factor Xa inhibitors, can prolong aPTT and/or PT. In the absence of an anticoagulant, evaluation for an underlying cause should include confirmation of the abnormal test, screening for nutritional deficiencies, liver function tests, and mixing studies to differentiate between a clotting factor deficiency and an inhibitor, as appropriate.

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Lupus anticoagulant hypoprothrombinemia syndrome (LA-HPS) is a rare, life-threatening bleeding complication that can occur in patients with positive LA tests, because of coexisting anti-prothrombin antibodies [18–20]. These patients are usually asymptomatic with a normal or slightly prolonged PT, but PT can become markedly prolonged when the prothrombin level is less than 30 % of normal [21]. Prolongation of PT discovered during preoperative assessment of an aPL-positive patient should prompt the physician to order a test for antibodies to prothrombin. For such patients, bleeding risk matches the INR in the same way it would if the patient were taking warfarin.

General Perioperative Considerations Antiphospholipid antibody-positive patients are at high risk of perioperative thrombosis secondary to withdrawal of chronic anticoagulation, increased hypercoagulability from multiple simultaneous thrombosis risk factors, and possibly the development of CAPS [22–24]. aPL-positive patients are, however, also at high risk of perioperative bleeding because of excessive anticoagulation, thrombocytopenia (present in 20 % of APS and 40 % of CAPS patients), and, uncommonly, highaffinity anti-prothrombin antibodies [1, 10, 18]. The risk of perioperative thrombosis can be reduced by taking the following steps: 1. minimize periods without anticoagulation; 2. restart postoperative anticoagulation as early as possible; 3. use physical methods in addition to pharmacologic methods; and 4. encourage postoperative ambulation and mobilization as early and as much as tolerated [19]. In addition, avoid limb tourniquets for extremity surgery, if possible, because these devices promote venous stasis and inhibit venous return. Despite optimum thrombosis prophylaxis, it is still possible for aPL-positive patients to develop vascular events so physicians should maintain a high index of suspicion. Physical thrombosis prophylaxis methods include gradual compression stockings (GCS) and intermittent pneumatic compression (IPC) devices, for example Venodyne compression sleeves. They prevent venous stasis, increase venous return, and increase tissue factor pathway inhibitor (TFPI) [25]. A Cochran review revealed that the combination of pharmacologic and mechanical prophylactic modalities reduce the incidence of all venous thromboembolism (VTE) compared with compression alone, and reduced the incidence of DVT, but not pulmonary embolism, compared with pharmacological prophylaxis alone [26]. Physical thrombosis

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prevention methods should be initiated during the surgery if possible and continued until the patient is completely mobile. Nurses, phlebotomists, and technicians should be involved in the perioperative management of aPL-positive patients. They should also understand and follow several steps to reduce thrombosis risk: 1. minimize intravascular manipulation, e.g., for access and monitoring; 2. when possible, avoid tourniquets when drawing blood; and 3. set pneumatic blood pressure cuffs to inflate infrequently to minimize stasis in the distal vascular bed [19]. For patients requiring physical therapy, the therapist should be informed about the increased thrombosis risk and the risk of bleeding secondary to anticoagulation. They should take precautions to prevent bruising, bleeding, and falls. Finally, all members of the team should observe aPL-positive patients very closely for signs and symptoms of thrombosis and maintain an extremely low threshold for investigation of possible blood clots.


continue for as long as possible while affording the flexibility to discontinue the effects of the medication quickly to prevent bleeding. Some guidelines suggest therapeutic doses of LMWH for patients at high risk of thrombosis because of substantial experience with this formulation of heparin for bridging; however, some physicians prefer IV UFH, because of ease of reversibility [30]. Table 2 summarizes a commonly used bridging anticoagulation protocol with LMWH for high-risk patients on chronic warfarin [30]. The schedule, which lasts approximately ten days, incorporates heparin while the INR is below a therapeutic range. Antiphospholipid antibody-positive patients with history of arterial and/or venous thrombosis who are on chronic warfarin sometimes have a higher target INR, e.g., greater than 3.0, instead of 2.0–3.0. In these cases, a longer period of warfarin interruption may be required. It may be necessary to discontinue warfarin one week in advance instead of five days in advance to reach subtherapeutic levels before surgery. Until a few years ago, warfarin was the outpatient anticoagulant of choice, but many newer anticoagulants are now available. Bridging guidelines should be adjusted on the basis of the washout periods of these medications. To date, there are no consensus recommendations, however.

Perioperative Anticoagulation Prophylactic Anticoagulation The three factors that contribute to thrombosis are hypercoagulability, stasis, and intimal injury [27]. Surgery predisposes patients to blood stasis secondary to immobilization and activates the clotting pathway by exposing tissue factor to circulating blood [28]. Surgery is a major thrombosis risk factor for any patient and aPL-positive patients are at especially high risk because of their underlying hypercoagulability. The need for a thrombosis prophylaxis plan and a specific anticoagulation regimen are determined by patients’ risk of thrombosis and by the type of surgery. Antiphospholipid antibody-positive patients are always considered to be at high risk of thrombosis and surgery is classified as low (e.g., dental or dermatological procedures), moderate (e.g., general, vascular, or major urologic surgery), or high (e.g., orthopedic or major trauma surgery) risk of thrombosis on the basis of on their complexity and duration [29]. Bridging “Bridging anticoagulation” refers to administration of a short-acting anticoagulant, for example subcutaneous lowmolecular-weight heparin (LMWH) or intravenous (IV) unfractionated heparin (UFH), around the time of surgery in place of the patient’s outpatient long-acting anticoagulation, for example warfarin. For APS patients on long-term anticoagulation, bridging is critical because it minimizes the risk of recurrent thrombosis. Transition to a short-acting agent enables anticoagulation to

Asymptomatic persistently aPL-positive patients with or without non-criteria aPL manifestations, and patients who were diagnosed on the basis of pregnancy morbidity alone are not necessarily at lower risk of perioperative thrombosis. These patients should also be managed aggressively during the Table 2 Summary of the bridging anticoagulation protocol with lowmolecular-weight heparin (LMWH) in the general population (modified from refs. [2••, 30]) −5 days −3 days

Discontinue warfarin Check INR and Kidney Function Start therapeutic dose LMWH (e.g., enoxaparin 1 mg/kg BID or 1.5 mg/kg QD) Adjust LMWH dose on the basis of creatinine clearance −24 hours Administer the last dose of LMWH 24 h before surgery (50 % of the dose for once-daily regimens) Day 0 Schedule for early morning surgery Check INR if needed If INR is still elevated (INR≥1.5), consider low-dose (1–2 mg) oral vitamin K Use aggressive perioperative mechanical DVT prophylaxis Start warfarin in the evening (regular dose) +24 hours Start prophylactic or therapeutic dose LMWH (can be delayed for 48–72 hours for patients undergoing high bleeding risk surgery) +4–5 days Discontinue LMWH when INR is therapeutic BID, twice daily; DVT, deep vein thrombosis; INR, international normalized ratio; QD, daily


perioperative period. The team should be aware that “moderate-to-high thrombosis risk” surgery, for example orthopedic or major trauma surgery, could induce the patient’s first venous or arterial event. If these patients are not already on chronic, outpatient anticoagulation, extended anticoagulation should be considered as soon as postoperative bleeding is controlled. The standard guidelines for patients at high risk of thrombosis should be the minimum dose and duration planned for these patients. Monitoring Antiphospholipid antibodies interfere with in-vitro tests of hemostasis by inhibiting the anchoring of coagulation proteins to phospholipid surfaces. For aPL-positive patients with an LA test that elevates the baseline aPTT, monitoring heparin dose can be problematic. Anti-factor Xa levels can be used instead of aPTT to ensure adequate anticoagulation. The most widely available test is the anti-factor Xa chromogenic assay, which is recommended by the College of American Pathologists. Monitoring should be performed four hours after heparin is injected or started when the anti-factor Xa activity peaks [31]. The target range is 0.5– 1.1 units/mL and 0.2–0.4 units/mL for therapeutic and prophylactic dose LMWH, respectively, but the range can vary depending on the heparin preparation and the dosing interval. Physicians should be aware that simultaneous aPTT and anti-Xa values are frequently discordant when used to measure UFH effects for patients [32, 33]. Epidurals Patients on perioperative anticoagulation are at risk of developing epidural or spinal hematomas when they undergo regional anesthesia with epidural catheters if the catheter is left in place to administer post-operative analgesia. Because many anesthesiologists prefer not to maintain an epidural catheter postoperatively in a patient on continuous intravenous heparin, it might be necessary to remove it immediately after surgery. Several organizations have released guidelines for management of anticoagulation in patients undergoing regional anesthesia; these should be discussed with the surgery and anesthesiology teams before the patient’s procedure, so the postoperative pain-management strategy can be planned in advance [34, 35].

Perioperative Bleeding In addition to thrombosis, the major risks associated with surgery for aPL-positive patients are bleeding and simultaneous bleeding and thrombosis. When aPL-positive patients bleed perioperatively, they remain at extremely high risk of

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thrombosis. Therefore, physical methods, for example intermittent pneumatic compression and/or gradual compression stockings, should be used aggressively. In addition, low-dose anticoagulation should be started as soon as bleeding is controlled, understanding that bleeding does not indicate that thrombosis will not occur although the risk of further bleeding remains high [36]. Many aPL-positive patients are on aspirin, which is often continued around the time of surgery. A recent randomized controlled trial illustrated that perioperative aspirin use had no significant effect on mortality or nonfatal myocardial infarction, but increased the risk of major bleeding [37]. However, this study did not consider aPL-positive patients; our recommendation is to continue aspirin during the perioperative period unless there is a high risk of bleeding. For patients with thrombocytopenia, platelet transfusions are often not effective as the mechanism of thrombocytopenia is believed to be peripheral destruction [16, 17]. Platelet transfusions can even increase the risk of thrombosis. Thus, platelet transfusions are not recommended unless bleeding is severe and life-threatening. High-dose corticosteroids and/or intravenous immunoglobulin (IVIG) are first-line agents [38]. Rituximab has also been used successfully to treat thrombocytopenia; however, the onset of action can vary substantially among patients [16, 39]. If an LA-positive patient with PT prolongation develops unexplained bleeding, high-dose corticosteroids should be started immediately, because they reduce the clearance of prothrombin–antithrombin antibody complexes and reduce anti-prothrombin antibody levels [18]. Factor replacement is not usually an option for these patients, because the mechanism of hypoprothrombinemia is destructive. For corticosteroid-resistant cases, immunosuppression with azathioprine, cyclophosphamide, or rituximab has been reported, and plasma exchange can be used to normalize prothrombin level [18, 21, 40]. Simultaneous bleeding and thrombosis is a challenging situation. A high index of suspicion of evolving CAPS is necessary [41]. Early diagnosis and aggressive therapy are essential for the survival of these patients. Severe thrombocytopenia resulting in bleeding should be managed with highdose corticosteroids and/or IVIG. The combination of anticoagulation, corticosteroids, and plasma exchange or intravenous immunoglobulin results in the best outcomes for CAPS [42]. When aPL-positive patients develop hemoptysis, hypoxemic respiratory failure, pulmonary infiltrates, and/or falling hemoglobin, diffuse alveolar hemorrhage (DAH) secondary to microthrombosis and/or pulmonary capillaritis should be strongly considered [43]. Diffuse alveolar hemorrhage is a life-threatening condition resulting from bleeding in the pulmonary microvasculature. It is a medical emergency, because delayed treatment can lead to significant morbidity and mortality, so physicians should have a low threshold to perform a

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bronchoscopy for diagnosis. The risk of recurrence is higher without immunosuppressive treatment and patients with acute DAH usually respond to corticosteroids [43]. Sudden hypotension, fever, and/or back pain during the perioperative period may indicate adrenal infarction and/or hemorrhage. In the absence of evidence-based guidelines, immediate use of parenteral corticosteroid replacement is recommended on the basis of the authors’ observations. Adrenal hemorrhage should be monitored by ultrasound or CT scan. It is not usually exsanguinating; in most instances, anticoagulation does not need to stop.

Special Considerations Emergency Surgery Emergency surgery for aPL-positive patients can be extremely challenging, because there is little time to devise perioperative strategies. Phytonadione or vitamin K can be used in general population patients taking vitamin K antagonists, for example warfarin, to reverse anticoagulation. For immediate reversal, fresh frozen plasma (FFP), prothrombin complex concentrate (PCC), or activated recombinant factor VII can be infused. In general, these agents should be avoided for aPL-positive patients unless there is life-threatening bleeding, because rapid reversal promotes immediate thrombosis and it may be difficult to achieve rapid therapeutic range anticoagulation after surgery. If needed, it is preferable to reverse slowly or partially. In addition, there have been reports of PCC-induced thrombosis [44]. Fresh frozen plasma, which contains all the coagulation factors, may also theoretically increase the risk of thrombosis. When reversal is absolutely necessary, the lowest possible dose of vitamin K (e.g. 1–2 mg instead of 5–10 mg) or FFP should be used with the understanding that it may take longer than expected to correct the anticoagulant effect for patients with a target INR of 3.0–4.0. Neurosurgery Anticoagulation for neurosurgery and spine surgery is problematic, because even minor bleeding can result in serious neurologic consequences. As a result, physical methods of prophylaxis are preferred for the general population [45]. Randomized trials, however, have demonstrated that lowdose UFH or LMWH are also effective for venous thromboembolism prophylaxis without excessive risk of bleeding [46]. According to the American College of Chest Physicians, postoperative prophylaxis with low-dose UFH or LMWH combined with GCS and/or IPC is preferred for patients with multiple thrombosis risk factors after neurosurgery. Although there are no evidence-based guidelines for the dose and timing of anticoagulation for aPL-positive patients undergoing


neurosurgery, preoperative INR should be lower than 1.5 if possible [47]. These patients require frequent neurologic examinations postoperatively. Renal Transplantation Antiphospholipid-positive patients are at high risk of renal allograft failure. In fact, patients with SLE and aPL are at increased risk of graft failure, morbidity, and mortality even in the absence of thrombosis history [48–51]. For patients without SLE, however, the effect of aPL is controversial, because some studies show a correlation between asymptomatic aPL positivity and graft failure and some do not [52, 53]. Routine determination of aPL is not necessary for all transplant recipients [54]. Anticoagulation before or during kidney transplantation has been shown to reduce the risk of post-transplantation thrombosis [55]. As a result, we recommend perioperative prophylactic dose heparin for aPL-positive patients not on long-term anticoagulation. In addition to anticoagulation, perioperative immunosuppressives can be beneficial for these patients, irrespective of histocompatability profiles; however, no systematic data are available [56]. Low-Risk Surgeries Procedures associated with a low risk of bleeding, for example minor dental procedures, cataract extractions, and skin biopsies, can usually be performed without stopping anticoagulation. For aPL-positive patients on long-term warfarin, INR can be maintained at approximately 2.0 on the day of the procedure. Inferior Vena Cava (IVC) Filters The utility of inferior vena cava (IVC) filters among aPLpositive patients is controversial, because both DVT and IVC thrombosis can result from the procedure itself and because thrombi often occlude the filter later [57, 58]. Therefore, physicians should have a high threshold for considering IVC filters in aPL-positive patients. They should be used only for patients with an acute lower extremity DVT in the setting of active bleeding.

Conclusions Perioperative management of aPL-positive patients is challenging because there are limited data on which to base recommendations. These patients are at high risk of thrombosis around the time of surgery so it is essential that medical and surgical teams devise a plan to minimize the patient’s risk of thrombosis without increasing risk of bleeding. During the perioperative period, pharmacological methods should be


combined with physical methods, patients should be closely observed for thrombosis, and any deviation from the normal course should be regarded as a potential aPL-related event. Periods without anticoagulation should be kept to an absolute minimum for aPL-positive patients with history of thrombosis, and physicians should keep in mind that thrombosis can occur despite optimum prophylaxis. We hope this article provides a basis enabling physicians to risk stratify patients, devise anticoagulation strategies, and address perioperative complications.

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11.•• Compliance with Ethics Guidelines Conflict of Interest Doruk Erkan declares that he has a paid consultancy with Alexion, and grants or grants pending from the Lupus Clinical Trials Consortium, the New York Community Trust, and Eli Lilly and Company. He has also received a speaker’s bureau honorarium from HGS. Katherine Saunders and Michael Lockshin declare that they have no conflict of interest. Human and Animal Rights and Informed Consent This article does not contain any studies with human or animal subjects performed by any of the authors.

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