Hospital Acquired Venous Thromboembolism: A Preventability Assessment.

Background: The American Heart Association has a call to action to reduce hospital acquired venous thromboembolism (HA-VTE) by 20% by the year 2030. There is increasing recognition that quality improvement initiatives for VTE reduction should focus on reducing potentially preventable HA-VTE. The objective of our study was to determine what proportion of HA-VTE events are potentially preventable. Methods: This was a retrospective, single center pilot study of 50 patients with HA-VTE. Seven preventability factors were identified with a focus on VTE prescription and administration. Data were extracted through chart review using a systematic data collection form. The primary endpoint was the proportion of patients with potentially preventable HA-VTE. Descriptive statistics were used. Results: The median age was 66 years with an admission VTE risk level of moderate-high in 94%. Potentially preventable HA-VTE was found in 40% of cases. Missed doses occurred in 29.8% with a median of 2 missed doses and a range of 1 to 20. Patient refusal was the most common reason for missed doses in 71%. Delays in initiation occurred in 12.7%. Sixty percent of those on mechanical prophylaxis only had nonadherence. Conclusion: Forty percent of HA-VTE cases were potentially preventable. Missed doses was the most common preventability factor identified with patient refusal accounting for most missed doses.

Anticoagulant drug-drug interactions with cannabinoids: A systematic review.

This systematic review evaluates the extent to which the effect of anticoagulants may be altered in the presence of cannabinoids. The following databases were searched: EMBASE, PubMed, Web of Science, Scopus, PscycINFO, and CINAHL from database inception through May 2023. Search terms included cannabis AND anticoagulant AND drug interactions and related keywords. The major outcome was hemorrhage or thrombosis and if available the relative change in quantitative intensity of anticoagulation after cannabinoid exposure. The search generated 959 citations. After the removal of 440 duplicates, 519 citations were screened. Overall, with the exception of warfarin, evidence supporting an interaction between cannabinoids and anticoagulants is non-existent. Seven case reports evaluating an interaction with warfarin were reported. Cannabis doses involved were either extremely high (e.g., >260 mg/day of delta-9-tetrahydrocannabidiol [THC] or >600 mg/day of cannabidiol [CBD]) or were not known. Hemorrhage was identified in 14.2% (1/7) of reports and thrombosis in 0%. Quantitative anticoagulation levels were increased in patients on warfarin (elevated International Normalized Ratio [INR]) in six of seven cases. A maximum INR change was available in five of seven reports, ranging from +0.4 to +9.61. One report found no change in INR after 4 days of medical cannabis exposure. Another report outlined two separate episodes of INR elevation associated with bleeding requiring hospitalization and reversal after marijuana smoking. Four cases involved reduction in weekly warfarin dose ranging from 22% to 31%. The Drug Information Probability Score was calculated in six cases, with a score of probable for five cases and possible for one. Very low-quality data support a potential drug-drug interaction with warfarin and both THC and CBD. Clinician recognition of this potential interaction is important. Available evidence supports the need to conduct a drug interaction study between cannabinoids and warfarin to clarify the existence of an interaction.

Potential Dexamethasone-Direct Oral Anticoagulant Drug Interaction: Is This a Concern in COVID?

OBJECTIVE: To evaluate the literature on a potential dexamethasone-direct oral anticoagulant (DOAC) drug interaction and provide management considerations with COVID hypercoagulability. DATA SOURCES: A search of EMBASE, PubMed, and Google Scholar (January 1990 to May 2021), limited to the English language, using applicable search terms resulted in 137 articles, with 21 relevant articles included. Regulatory agency and clinical guidance documents were also reviewed. STUDY SELECTION AND DATA EXTRACTION: Included articles describe in vitro or in vivo animal or human data for dexamethasone induction of cytochrome P450 (CYP) 3A4 or P-glycoprotein (P-gp). DATA SYNTHESIS: Dexamethasone has the potential to interact with the DOACs via CYP3A4 and/or P-gp induction. Only apixaban and rivaroxaban have CYP3A4 metabolism. Dexamethasone can increase CYP3A4 activity by up to 70% and reduce the area under the concentration-time curve (AUC) of CYP3A4 substrates by >40%, which is consistent with criteria for a weak CYP inducer. In rodents, dexamethasone P-gp induction is associated with AUC reductions of 20% to 50%. Human data are lacking. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Severe COVID-19 infection is associated with hypercoagulability. Although heparins are the preferred anticoagulants for hospitalized COVID-19 patients, DOACs are being utilized. Dexamethasone is recommended for hospitalized COVID-19 patients requiring supplemental oxygen. The concurrent use of dexamethasone and apixaban or rivaroxaban in such patients carries the potential for reduced anticoagulant effect during a state of heightened thrombotic risk. CONCLUSIONS: Concurrent use of dexamethasone and apixaban or rivaroxaban in hospitalized COVID-19 patients with laboratory evidence of COVID coagulopathy should be avoided until higher-quality data are available.

Serotonin-release assay-positive but platelet factor 4-dependent enzyme-immunoassay negative: HIT or not HIT?

IgG-specific and polyspecific PF4-dependent enzyme-immunoassays (EIAs) have exceptionally high sensitivity (≥99%) for diagnosis of heparin-induced thrombocytopenia (HIT), a drug reaction caused by platelet-activating antibodies detectable by serotonin-release assay (SRA). The IgG-specific EIAs are recommended for screening, as their high sensitivity is accompanied by relatively high specificity vis-à-vis polyspecific EIAs. We investigated the frequency of SRA-positive/EIA-negative (SRA+/EIA-) HIT, prompted by referral to our reference HIT laboratory of serial blood samples from a patient ("index case") with false-negative IgG-specific EIAs. Despite initial clinical suspicion for HIT, repeat negative IgG-specific EIAs prompted heparin resumption, which triggered recurrent thrombocytopenia and near-fatal cardiac arrest, indicating likely post-heparin HIT-associated anaphylactoid reaction. Further investigations revealed a strong-positive SRA, whether performed with heparin alone, PF4 alone, or PF4/heparin, with inhibition by Fc receptor-blocking monoclonal antibody (indicating IgG-mediated platelet activation); however, five different IgG-specific immunoassays yielded primarily negative (or weak-positive) results. To investigate the frequency of SRA+/EIA- HIT, we reviewed the laboratory and clinical features of patients with this serological profile during a 6-year period in which our reference laboratory investigated for HIT using both SRA and IgG-specific EIA. Although ~0.2% of 8546 patients had an SRA+/EIA- profile, further review of 15 such cases indicated clerical/laboratory misclassification or false-positive SRA in all, with no SRA+/EIA- HIT case identified. We conclude that while SRA+/EIA- HIT is possible-as shown by our index case-this clinical picture is exceptionally uncommon. Moreover, the requirement for a positive EIA is a useful quality control maneuver that reduces risk of reporting a false-positive SRA result.

Timing of Initiation of Oral Anticoagulation after Acute Ischemic Stroke in Patients with Atrial Fibrillation.

Patients with atrial fibrillation (AF) who suffer an acute ischemic stroke are at risk for both hemorrhagic transformation and recurrent ischemic stroke in the acute post-stroke period. Oral anticoagulants are recommended for secondary stroke prevention in patients with AF. The optimal time to initiate anticoagulant therapy after acute ischemic stroke in patients with AF is uncertain. There is concern that early initiation increases the risk of hemorrhagic transformation, whereas delayed initiation leaves the patient at risk for recurrent ischemic stroke. In this article, we provide a review of the risk of hemorrhagic transformation of acute ischemic stroke as well as review the literature and major guidelines addressing the timing of anticoagulation initiation after an acute ischemic stroke in patients with AF. Relevant articles published from 1990 to the present were identified using the PubMed and Embase databases. The majority of available literature is observational data. Large ischemic lesions, cerebral microbleeds, thrombolytic therapy, and other clinical factors may increase the risk of hemorrhagic transformation of an acute ischemic stroke. Parenteral anticoagulation within 48 hours is associated with an increased risk of hemorrhagic transformation and is not recommended. Insufficient data exist to support the safety of routine oral anticoagulant (direct oral anticoagulants or warfarin) initiation within 48 hours of an acute ischemic stroke. Direct oral anticoagulant initiation within 2 days of an acute ischemic stroke is associated with a 5% rate of hemorrhagic transformation. Infarct size and presence of hemorrhage are important factors in identifying the optimal time to initiation and should guide decisions when available. A recommended framework for patient decision making is provided. Randomized controlled trials in this area are needed to identify the optimal timing of anticoagulation initiation, and such trials are under way.

American Society of Hematology 2019 guidelines for management of venous thromboembolism: prevention of venous thromboembolism in surgical hospitalized patients.

BACKGROUND: Venous thromboembolism (VTE) is a common source of perioperative morbidity and mortality. OBJECTIVE: These evidence-based guidelines from the American Society of Hematology (ASH) intend to support decision making about preventing VTE in patients undergoing surgery. METHODS: ASH formed a multidisciplinary guideline panel balanced to minimize bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline-development process, including performing systematic reviews. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess evidence and make recommendations, which were subject to public comment. RESULTS: The panel agreed on 30 recommendations, including for major surgery in general (n = 8), orthopedic surgery (n = 7), major general surgery (n = 3), major neurosurgical procedures (n = 2), urological surgery (n = 4), cardiac surgery and major vascular surgery (n = 2), major trauma (n = 2), and major gynecological surgery (n = 2). CONCLUSIONS: For patients undergoing major surgery in general, the panel made conditional recommendations for mechanical prophylaxis over no prophylaxis, for pneumatic compression prophylaxis over graduated compression stockings, and against inferior vena cava filters. In patients undergoing total hip or total knee arthroplasty, conditional recommendations included using either aspirin or anticoagulants, as well as for a direct oral anticoagulant over low-molecular-weight heparin (LMWH). For major general surgery, the panel suggested pharmacological prophylaxis over no prophylaxis, using LMWH or unfractionated heparin. For major neurosurgery, transurethral resection of the prostate, or radical prostatectomy, the panel suggested against pharmacological prophylaxis. For major trauma surgery or major gynecological surgery, the panel suggested pharmacological prophylaxis over no prophylaxis.

Major bleeding with apixaban in atrial fibrillation: patient characteristics, management, and outcomes.

OBJECTIVES: To identify patient characteristics, bleed management, and bleed outcomes in patients experiencing an apixaban major bleeding event and to identify opportunities to improve the safe use of apixaban. METHODS: This retrospective single health-system study identified apixaban patients experiencing a major bleeding event between January 2013 and May 2016 through electronic medical record review. Patient characteristics, bleed management, and outcomes were extracted in those with a confirmed major bleed assessed by the International Society on Thrombosis and Haemostasis criteria. RESULTS: Fifty major bleeding events occurred in 49 patients (79 ± 9.8 years). Patient characteristics included history of hypertension (94%), anemia (68%), and concomitant antiplatelet use (68%). Gastrointestinal bleeding occurred in 72% of patients and intracranial hemorrhage in 14% of patients. Packed red blood cells (PRBCs) were utilized in 82% of patients and reversal agents were administered to 6% of patients. Mortality during the hospital admission for the bleed was 0%. Anticoagulation was held at discharge in 64% of patients and remained held at 30 days in the majority of patients. Of those on concurrent aspirin therapy, an appropriate indication was not found in 64.7% of patients. CONCLUSIONS: Patients with major bleeding were elderly and frequently on inappropriate concomitant antiplatelet therapy. The majority of patients were managed with PRBC transfusion. More than half of patients had anticoagulation therapy held at discharge. Concerns with prescribing and patient management were identified leading to recommendations for improving the safe use of apixaban therapy.

Characteristics, Management, and Outcomes of Patients with Atrial Fibrillation Experiencing a Major Bleeding Event While on Rivaroxaban.

Rivaroxaban, the first oral direct factor Xa inhibitor, was approved for stroke prevention in nonvalvular atrial fibrillation in 2011. Limited data are available regarding major bleeding in a clinical practice setting. The purpose of this study is to describe the patient characteristics, management, and outcomes of major bleeding events in patients receiving rivaroxaban for atrial fibrillation. This retrospective, single health system study identified patients with rivaroxaban having a major bleeding event between July 2011 and June 2014. Patients were identified through adverse event reporting or by cross-referencing rivaroxaban with International Classification of Diseases, Ninth Revision diagnosis codes for atrial fibrillation and hemorrhage, with and without transfusion. A total of 60 patients were identified. The mean age of patients was 80.3 ± 7.4 years. The most common bleed sites were gastrointestinal (63.3%) and intracranial (26.7%). Higher dose than recommended based on renal function was present in 35% of patients and concurrent antiplatelet therapy occurred in 70%. Activated prothrombin complex concentrate was utilized in 30% of patients and recombinant factor VIIa in 6.7%. A procedure or surgery was performed for bleed management in 10 patients. Anticoagulation was held at discharge in 76% of patients. A total of 6 patients died during hospital admission, 5 of whom experienced an intracranial hemorrhage. In conclusion, patients experiencing a rivaroxaban major bleeding event were elderly, often renally impaired, and receiving concurrent antiplatelet therapy. In-hospital mortality was 10%. The majority of patients (76%) had anticoagulation therapy held at discharge.

Reversal agents for use with direct and indirect anticoagulants.

PURPOSE: The properties of three oral anticoagulant-specific reversal agents are reviewed, and guidance is presented to assist pharmacists in planning for the agents' introduction to the market. SUMMARY: Idarucizumab, which received Food and Drug Administration approval in October 2015, is a humanized monoclonal antibody fragment that immediately neutralizes the anticoagulant effect of dabigatran, as evidenced by reduced unbound dabigatran concentrations and normalized coagulation tests. Preliminary Phase III trial results demonstrated a median maximum reversal of 100%, a median time to bleeding cessation of 11.4 hours, and normal intraoperative hemostasis in 92% of patients requiring anticoagulation reversal before an urgent procedure. Andexanet alfa is a factor Xa (FXa) decoy that binds to direct and indirect FXa inhibitors. In Phase III trials in healthy volunteers, andexanet alfa reduced anti-FXa activity by more than 90%, reduced the concentration of unbound direct FXa inhibitor, and inhibited thrombin generation. Ciraparantag is a reversal agent under development for reversal of anticoagulation with direct and indirect FXa inhibitors and certain factor IIa inhibitors; it exerts its effect through hydrogen bonding. Concerns for thromboembolic events directly related to administration of idarucizumab, andexanet alfa, or ciraparantag have not arisen. Pharmacists need to begin preparing for the introduction of these specific reversal agents through protocol development and provider education; in addition, pharmacy departments need to plan for procurement and storage. The specific reversal agents should be incorporated into antithrombotic stewardship or other clinical pharmacy programs for surveillance. CONCLUSION: As agents that provide rapid reversal of direct oral anticoagulant activity become available, advance planning will help hospitals to optimize their use.

Guidance for the practical management of the heparin anticoagulants in the treatment of venous thromboembolism.

Venous thromboembolism (VTE) is a serious and often fatal medical condition with an increasing incidence. Despite the changing landscape of VTE treatment with the introduction of the new direct oral anticoagulants many uncertainties remain regarding the optimal use of traditional parenteral agents. This manuscript, initiated by the Anticoagulation Forum, provides clinical guidance based on existing guidelines and consensus expert opinion where guidelines are lacking. This specific chapter addresses the practical management of heparins including low molecular weight heparins and fondaparinux. For each anticoagulant a list of the most common practice related questions were created. Each question was addressed using a brief focused literature review followed by a multidisciplinary consensus guidance recommendation. Issues addressed included initial anticoagulant dosing recommendations, recommended baseline laboratory monitoring, managing dose adjustments, evidence to support a relationship between laboratory tests and meaningful clinical outcomes, special patient populations including extremes of weight and renal impairment, duration of necessary parenteral therapy during the transition to oral therapy, candidates for outpatient treatment where appropriate and management of over-anticoagulation and adverse effects including bleeding and heparin induced thrombocytopenia. This article concludes with a concise table of clinical management questions and guidance recommendations to provide a quick reference for the practical management of heparin, low molecular weight heparin and fondaparinux.

Optimizing Anticoagulation Management Through the Use of a Hospital Engagement Network Metric for Inpatient Anticoagulant-Associated Hemorrhage.

BACKGROUND: The University HealthSystem Consortium (UHC), a national hospital engagement network (HEN), establishes health-system metrics to assess and improve quality of care. In 2012, a metric for inpatient anticoagulant hemorrhage was developed. The utility of this metric to improve anticoagulation care has not been assessed. OBJECTIVE: To identify opportunities to improve anticoagulation safety through the use of a HEN metric for inpatient anticoagulant-associated hemorrhage. METHODS: This was a single-center, retrospective, observational study of metric identified patients with presumed inpatient anticoagulant hemorrhage. Records were reviewed to confirm anticoagulant hemorrhage and identify bleed site and severity. A structured process was used to assess bleed preventability and subsequently identify opportunities for improving care. Each bleed was reviewed by 2 investigators. RESULTS: Anticoagulant hemorrhage was confirmed in 85.9% (61/71) with heparin infusion the most common anticoagulant. Patients were primarily medical, with a mean age of 72.7 ± 15 years. The most common bleed sites were gastrointestinal (24.6%) and retroperitoneal (21.3%). Major bleeding occurred in 60.7% (37/61). Anticoagulant hemorrhage was preventable in 18% (11/61) of cases with heparin protocol noncompliance the most common cause of a preventable bleed. Several opportunities for improving heparin infusion therapy were recognized and protocol changes were implemented. CONCLUSIONS: The UHC metric accurately captures inpatient anticoagulant-associated hemorrhage the majority of time. The UHC metric on anticoagulant-associated hemorrhage can be a useful part of a health system's overall plan for the safe use of anticoagulants in the hospital setting.

Dabigatran versus warfarin major bleeding in practice: an observational comparison of patient characteristics, management and outcomes in atrial fibrillation patients.

Data comparing the patient characteristics, management and outcomes for dabigatran versus warfarin major bleeding in the practice setting are limited. We performed a retrospective single health system study of atrial fibrillation patients with dabigatran or warfarin major bleeding from October 2010 through September 2012. Patient identification occurred through both an internal adverse event reporting system and a structured stepwise data filtering approach using the International Classification of Diseases diagnosis codes. Thirty-five dabigatran major bleeding patients were identified and compared to 70 warfarin major bleeding patients. Intracranial bleed occurred in 4.3 % of warfarin patients and 8.6 % of dabigatran patients. Dabigatran patients tended to be older (79.9 vs. 76 years) and were more likely to have a creatinine clearance of 15-30 mL/min (40 vs. 18.6 %, p = 0.02). Over one-third of dabigatran patients had an excessive dose based on renal function. More dabigatran patients required a procedure for bleed management (37.1 vs. 17.1 %, p = 0.03) and received a hemostatic agent for reversal (11.4 vs. 1.4 %, p = 0.04). Dabigatran patients were twice as likely to spend time in an ICU (45.7 vs. 27.1 %, p = 0.06), be placed in hospice/comfort care (14.3 vs. 7.1 %, p = 0.24), expire during hospitalization (14.3 vs. 7.1 %, p = 0.24), and expire within 30-days (22.9 vs. 11.4 %, p = 0.28). In a single hospital center practice setting, as compared to warfarin, patients with dabigatran major bleeding were more likely to be older, have renal impairment, require a procedure for bleed management and receive a hemostatic agent. Patients with dabigatran major bleeding had an excessive dose for renal function in more than one-third of cases.

Rivaroxaban: practical considerations for ensuring safety and efficacy.

Rivaroxaban is the first agent available within a new class of anticoagulants called direct factor Xa inhibitors. Rivaroxaban is approved for use in the United States for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, for the prevention of deep vein thrombosis in patients undergoing total hip replacement and total knee replacement, for the treatment of deep vein thrombosis and pulmonary embolism, and for the reduction in risk of recurrence of deep vein thrombosis and pulmonary embolism (with additional indications under review). Rivaroxaban dose and frequency of administration vary depending on the indication. As of result of predictable pharmacokinetics and pharmacodynamics, a fixed dose of rivaroxaban is administered without routine coagulation testing. Rivaroxaban has a short half-life, undergoes a dual mode of elimination (hepatic and renal), and is a substrate for P-glycoprotein. Rivaroxaban has a lower potential for drug interactions compared with warfarin. Despite the advantages of a once/day fixed-dose oral agent, in many clinical situations limited evidence is available to guide optimal management of rivaroxaban therapy. In this article, we review the available evidence and provide recommendations where possible for such situations including the desire to monitor the anticoagulation intensity, use in special patient populations, managing drug interactions, and transitioning across anticoagulant agents. Potential strategies for reversing rivaroxaban's anticoagulant effect are reviewed. Health systems will need to perform a systematic safety evaluation and ensure that numerous hospital policies related to anticoagulation are updated to include rivaroxaban. A comprehensive approach to education is needed for clinicians, patients, and technical support personnel involved in patient interactions to ensure safe use.

Assessing the impact of a heparin-induced thrombocytopenia protocol on patient management, outcomes and cost.

Establishing the diagnosis of heparin induced thrombocytopenia (HIT) is challenging as laboratory tests for HIT vary in specificity and availability. As HIT suspicion far exceeds confirmation of diagnosis, overtreatment is an emerging concern. This pilot study evaluated the impact of a HIT Recognition and Management Protocol on direct thrombin inhibitor (DTI) prescribing, outcomes, and cost. The primary endpoint was DTI cessation within 12 hours of receipt of negative HIT serology. An observational cohort study using a pre-post design was performed. Sixty-one patients were in the pre-period (before implementation) and 46 in the post-period (after implementation). DTI therapy was discontinued within 12 hours of negative serology in 19.4% of pre-period patients compared to 40% of post-period patients, p=.058. DTI therapy was discontinued within 24 hours of receipt of a negative PF4/heparin ELISA more often in the post-period; 7/23 (30.4%) pre-period patients versus 16/26 (61.5%) post-period patients, p <0.05. Protocol implementation resulted in a significant improvement in timely initiation of DTI therapy (within 12 hours of HIT antibody testing) in those with a moderate to high suspicion of HIT; 8/31 (25.8%) of pre-period patients versus 24/31 (77.4%) of post-period patients, p <0.0001. Thrombotic events occurred in significantly more patients in the pre-period as compared to the post-period; 21/61 (34.4%) versus 6/46 (13%), respectively, p = 0.01. Major bleeding was reduced by 6.6 % after protocol implementation. The projected annual cost savings from decreased inappropriate DTI use was over $450,000. Protocol implementation had a positive impact on DTI prescribing, outcomes and cost.

Development and implementation of a comprehensive heparin-induced thrombocytopenia recognition and management protocol.

PURPOSE: A quality initiative to improve the management of heparin-induced thrombocytopenia (HIT) at an academic medical center, including the development of guidelines on the use of direct thrombin inhibitors (DTIs), is described. SUMMARY: In keeping with the Joint Commission's National Patient Safety Goal (NPSG) for anticoagulant therapy (goal 03.05.01), a multidisciplinary working group conducted a needs assessment to identify areas for improvement in the center's HIT management practices, particularly the use of DTI therapy (an issue not specifically addressed by NPSG 03.05.01). The resulting action steps included (1) the implementation of a detailed protocol for the recognition and management of HIT, as well as guidelines on the use of the DTIs argatroban and lepirudin, (2) more efficient use and optimized documentation of initial and confirmatory tests in the electronic medical record (EMR), and (3) the education of pharmacists, nurses, and physicians on the use of the HIT protocol, with initial and ongoing case-based competency testing of pharmacy staff. Early postimplementation experience indicated that the protocol and associated activities have resulted in improved DTI prescribing and dosing, HIT documentation, and patient education practices while expanding pharmacists' involvement in ensuring optimal, cost-effective management of patients with HIT. CONCLUSION: In one institution, an HIT working group extended the scope of NPSG 03.05.01 to include the parenteral DTIs. The implementation of the HIT protocol has resulted in greater compliance with appropriate DTI dosing and improved EMR documentation of HIT.

Strategies for managing heparin therapy in patients with antiphospholipid antibody syndrome.

Antiphospholipid antibody syndrome (APS) is a common acquired thrombophilia. The diagnosis of APS is based on both clinical and laboratory criteria. The clinical criteria include vascular thrombosis or pregnancy morbidity. The laboratory criteria include a positive test for lupus anticoagulant, anticardiolipin antibodies, or anti-ß(2)-glycoprotein I (anti-ß(2)GPI) antibodies on two or more occasions at least 12 weeks apart. Antiphospholipid antibodies with lupus anticoagulant activity may prolong phospholipid-dependent coagulation tests such as the activated partial thromboplastin time (aPTT) and the activated clotting time (ACT). This prolongation adds a level of complexity to monitoring heparin therapy in patients with APS who have thrombosis. A literature search of the PubMed database was conducted for relevant articles published from 1995-April 2011. The usual management approach in nonsurgical patients with APS is to switch to low-molecular-weight heparin. In patients in whom heparin remains the agent of choice, management options include monitoring heparin antifactor Xa levels, determining an individualized therapeutic aPTT range, targeting an aPTT goal of 2 times the baseline aPTT, or using an aPTT reagent insensitive to lupus anticoagulant. An algorithm for anticoagulation management in nonsurgical patients with APS who require heparin is provided. The strategies to monitor intraoperative heparin in patients undergoing cardiac surgery include measuring heparin concentrations by an automated protamine titration device, targeting twice the baseline ACT, using preoperative in vitro heparin-ACT titration curves, and measuring heparin antifactor Xa levels. The available published case reports on the use of these strategies are reviewed. Each institution should determine an approach to managing heparin in patients with APS that best meets its needs and resources.