Is there literature to support various forms of anticoagulation in patients who have durable and temporary cardiac devices (i.e., LVAD)?

Comment by InpharmD Researcher

Available data consistently suggest comprehensive anticoagulation management in LVAD patients. The standardized approach for postoperative chronic anticoagulation commonly includes vitamin K antagonists with target INR varying from 2.0 to 3.0. The potential of DOACs as viable alternatives to warfarin has been studied; however, DOACs are not currently recommended as primary anticoagulation in LVADs due to safety concerns.

The 2019 European Association for Cardio-Thoracic Surgery (EACTS) consensus statement on long-term mechanical circulatory support (LT-MCS) recommends withdrawal of dual antiplatelet therapy and/or vitamin K antagonists to reduce the risk of bleeding and to optimize preoperative organ function. It also supports the use of short-acting intravenous (IV) anticoagulation for bridging prior to implantation of LT-MCS. IV antithrombotics are specifically recommended for preoperative conditions. Postoperative early anticoagulation is mentioned as being mandatory, with IV unfractionated heparin (UFH) being a commonly used agent. Anticoagulation can be initiated 8 hours after surgery with all devices if bleeding is less than 50 mL/hour with an initial target activated partial thromboplastin time of 40 seconds. Target activated partial thromboplastin time is then increased to 55-60 seconds over the first 48-72 hours. The vitamin K antagonist can be initiated once the clinical condition is stable and oral administration is possible. The target INR varies from 2.0 to 3.0 depending on device recommendations. Aspirin (acetylsalicylic acid) is routinely used. This consensus statement does not currently recommend the use of direct oral anticoagulants (DOACs). [1]

The 2013 International Society for Heart and Lung Transplantation (ISHLT) guidelines for mechanical circulatory support recommend IV heparin or alternative anticoagulation if there is no evidence of bleeding on a postoperative day 1 to 2 for the management of HeartMate II patients. Heparin can be continued, or warfarin and aspirin (81 to 325 mg daily) can be started after the removal of chest tubes on a postoperative day 1 to 3. The same recommendations are made for patients receiving implantable centrifugal pumps or pulsatile mechanical circulatory support devices. [2] Consistently, American Heart Association (AHA) Scientific Statement discussed that the current generation of continuous-flow ventricular assist devices (CF-VADs) may require both systemic anticoagulation and antiplatelet therapy. [3]

Per institution-based practice guidelines specific to antithrombotic management of patients with left ventricular assist systems (LVAS), the standardized approach for comprehensive anticoagulation management of these patients is divided into 3 phases of care including: (1) perioperative anticoagulation management during the initial hospitalization for LVAS placement, (2) subsequent inpatient admissions, and (3) routine outpatient management. The postoperative inpatient management recommends antiplatelet and anticoagulation strategies for the early postoperative period which include initiation of warfarin based on risk factors for bleeding and warfarin sensitivity (e.g., age, liver dysfunction, nutritional status, history of warfarin dosing, drug-drug interactions). Once hemostasis is achieved, antiplatelet therapy (postoperative day [POD] 0) in conjunction with IV anticoagulation as a bridge to a therapeutic INR (typically PODs 1-3) should be considered. IV anticoagulation with direct thrombin inhibitor (bivalirudin) is reserved for those with a history of heparin-induced thrombocytopenia (HIT) or in bridge-to-transplant (BTT) status. For routine outpatient management, fondaparinux could be considered for patients with a history of HIT, or in BTT patients to decrease exposure to heparin products and possible development of HIT antibodies prior to transplant. Anticoagulation therapy should be individualized based on the patient’s history of bleeding or recurrence risk of thrombotic events. [4]

A comprehensive state-of-the-art review on antiplatelet and anticoagulation strategies for left ventricular assist devices (LVAD) discussed pre-implant, intraoperative, and perioperative anticoagulation management for patients undergoing LVAD. For pre-implant anticoagulation management, outpatients taking direct oral anticoagulants (DOACs) should be transitioned to coumadin or bridged with heparin/enoxaparin, and outpatients on coumadin should be bridged with unfractionated heparin (UFH). Subsequent discontinuation of low molecular weight heparin (LMWH) and fondaparinux should proceed 12 and 24 hours prior to the surgery, respectively. For intraoperative anticoagulation management during cardiopulmonary bypass (CPB), UFH is most commonly used given its short half-life and availability of a reversal agent. There is a lack of clear consensus on initial UFH dose calculations, but some options include a fixed, weight-based dose (e.g., 300 IU/kg) and the use of point-of-care tests that measure the whole blood sensitivity to heparin using an associated dose-response. For perioperative anticoagulation management, the manufacturer guidelines exist [Table 1], but there are variations between institutions. UFH bridging to a therapeutic vitamin K antagonist (VKA) is recommended after LVAD implantation. The potential of DOACs as viable alternatives to warfarin in LVAD patients was discussed; however, given the safety concerns, DOACs are not currently recommended as primary anticoagulation in LVADs. [5]

A 2017 retrospective analysis evaluated the proportion of time spent in target range (PTTR) for INR (estimated target range of 2.0 to 3.0) among adult patients (N= 115) with LVAD placed from 2006 to 2012. During 624.5 months of follow-up, LVAD patients remained in the INR target range for an average of 42.9% of the time. The finding is consistent with the result shown in the previous small case series (N= 16) which also demonstrated low rates of anticoagulation control despite the rigorous anticoagulation and VAD management. The authors noted that when compared to other chronically anticoagulated patients such as those with nonvalvular atrial fibrillation (proportion of time spent in target range [PTTR] 68%), the percent time in range appeared less in VAD patients. [6-7]


1] Potapov EV, Antonides C, Crespo-Leiro MG, et al. 2019 EACTS Expert Consensus on long-term mechanical circulatory support. Eur J Cardiothorac Surg. 2019;56(2):230-270. doi:10.1093/ejcts/ezz098
[2] Feldman D, Pamboukian SV, Teuteberg JJ, et al. The 2013 International Society for Heart and Lung Transplantation guidelines for mechanical circulatory support: executive summary. J Heart Lung Transplant. 2013;32(2):157-187. doi:10.1016/j.healun.2012.09.013
[3] Peura JL, Colvin-Adams M, Francis GS, et al. Recommendations for the use of mechanical circulatory support: device strategies and patient selection: a scientific statement from the American Heart Association. Circulation. 2012;126(22):2648-2667. doi:10.1161/CIR.0b013e3182769a54
[4] Levesque AA, Lewin AR, Rimsans J, et al. Development of multidisciplinary anticoagulation management guidelines for patients receiving durable mechanical circulatory support. Clin Appl Thromb Hemost. 2019;25:1076029619837362. doi:10.1177/1076029619837362
[5] Loyaga-Rendon RY, Kazui T, Acharya D. Antiplatelet and anticoagulation strategies for left ventricular assist devices. Ann Transl Med. 2021;9(6):521. doi:10.21037/atm-20-4849
[6] Boehme AK, Pamboukian SV, George JF, et al. Anticoagulation control in patients with ventricular assist devices. ASAIO J. 2017;63(6):759-765. doi:10.1097/MAT.0000000000000592
[7] Jennings D, McDonnell J, Schillig J. Assessment of long-term anticoagulation in patients with a continuous-flow left-ventricular assist device: a pilot study. J Thorac Cardiovasc Surg. 2011;142(1):e1-2. doi: 10.1016/j.jtcvs.2011.03.029

Literature Review

A search of the published medical literature revealed 7 studies investigating the researchable question:

Is there literature to support various forms of anticoagulation in patients who have durable and temporary cardiac devices (i.e., LVAD)?

Please see Tables 1-7 for your response.


LVAD Manufacturer Recommendations

  Perioperative heparin Platelet initiation  Anticoagulatoin initiation 

Maintenance regimen

Heartmate II (1)

If no persistent bleeding, begin bridging with unfractionated heparin or LMWH within 48 hours of device implant with a goal PTT of 40–45 sec in the first 48 hours, followed by a titration up to PTT 50–60 by 96 hours

Once no evidence of bleeding, initiate ASA therapy (81–325 mg daily) 2 to 5 days post HMII implantation Initiate warfarin within 48 hours to obtain a goal INR of 2.0–2.5 by POD 5–7, then discontinue heparin Maintain the patient throughout LVAD support on aspirin and Coumadin with a goal INR of 2.0–2.5
Heartware (2)

Begin low-dose heparin at 10 units/kg/hr on postoperative day one to a target PTT of 40–50 seconds. Prior to initiation of anticoagulation, chest tube drainage should be less than 40 mL/hr for approximately three hours; the HCT should be stable without the need for transfusion of blood products, and coagulation factors approaching normal. Gradually increase the heparin dosage to maintain the aPTT in a range of 50–60 seconds

Aspirin should be started at a dose such as 325 mg/d within 24 hours after implant if no postoperative bleeding complications. If ASA alone chosen, check for ASA resistance is recommended to establish the dose or to select an alternative. For patients who are aspirin sensitive or intolerant, clopidogrel at doses of 75–150 mg/day (after a load of 300 mg) Warfarin should be started within 4 days post-op and titrated to maintain an INR of 2.0 to 3.0

Maintain anticoagulation for INR range of 2.0–3.0

Daily aspirin dose should be >81 mg and platelet inhibition should be evaluated and adjust ASA mono-therapy accordingly or consider combination therapy such as ASA 81 mg plus Aggrenox (ASA plus extended-release dipyridamole) or daily ASA 81 mg plus Plavix 75 mg

Heartmate 3 (3)

Begin IV heparin after 12–24 hours or when chest tube drainage is less than 50 mL/hr over a 2–3 hours period:

• Initially titrate to a PTT of 45–50 for 24 hours (1.2–1.4 times control)

• After 24 hours, increase heparin and titrate to PTT 50–60 (1.4–1.7 times control)

• After another 24 hours, increase heparin and titrate to PTT 55–65 (1.5–1.8 times control)

On postoperative day 2–3, initiate ASA 81–100 mg QD On postoperative day 3–5, once there is no evidence of bleeding and the chest tubes have been removed, begin warfarin (overlapping with the heparin). Discontinue heparin after obtaining an acceptable, stable INR. The INR should be maintained in the range of 2.0–3.0 Maintain the patient throughout support on aspirin and warfarin

PT, prothrombin time; PTT, partial thromboplastin time; LMWH, low molecular weight heparin; HMII, Heartmate II; INR, international normalized ratio.




[1] Corporation T. Heartmate II Instructions for Use. 2017. Available online:
[2] Corportation H. Heartware HVAD IFU. Available online:
[3] Corporation A. Heartmate III Instructions for Use 2019. Available online:


PREVENtion of HeartMate II Pump Thrombosis Through Clinical Management: The PREVENT Multi-center Study


Prospective, multicenter, single-arm, non-randomized study

N= 300


To evaluate outcomes in patients with the adoption of PREVENT recommendations aimed at reducing the risk of pump thrombosis (PT)

Study Groups

HeartMate II patients (N= 300)

Inclusion Criteria

Consecutive patients age ≥ 18 years receiving HeartMate II (HMII) in accordance with Food and Drug Administration-approved indications and as their first left ventricular assist device (LVAD)

Exclusion Criteria

Existence of ongoing mechanical circulatory support (other than intraaortic blood pump), pregnancy, participation in any other clinical trial investigations that would confound results of the study


All centers enrolled in the trial were expected to adopt and adhere to PREVENT recommendations, which were aimed at maximizing flow through the LVAD, reducing the risk of cannula malposition, and ensuring patients are adequately anti-coagulated while on LVAD support. Deviations from the recommendations were allowed as deemed necessary by clinical judgment in specific cases. Patients with a previous thromboembolic event or at risk of a thromboembolic event could be managed with a higher international normalized ratio (INR) target or with additional antiplatelet therapy. Patients with bleeding events or at higher risk for bleeding could use lower target anticoagulation and/or reduced antiplatelet therapies.

The PREVENT recommendations for anticoagulation and antiplatelet management include:

1. In patients without persistent bleeding, begin bridging with unfractionated heparin or low-molecular-weight heparin (LMWH) within 48 hours of device implantation with a goal partial thromboplastin time (PTT) of 40 to 45 seconds in the first 48 hours, followed by a titration up to PTT of 50 to 60 seconds by 96 hours. If heparin is contraindicated, consider other alternatives, including argatroban, intravenous warfarin, and bivalirudin.

2. Initiate warfarin within 48 hours to obtain goal INR of 2.0 to 2.5 by postoperative days 5 to 7, at which time heparin therapy may be discontinued.

3. When there is no evidence of bleeding, initiate aspirin therapy (81 to 325 mg daily) 2 to 5 days after HMII implantation.

4. Maintain the patient throughout LVAD support on aspirin and warfarin with a goal INR of 2.0 to 2.5.


Enrollment: September 24, 2014, to November 5, 2015

Follow-up: 6 months

Outcome Measures

Primary outcome: confirmed PT at 3 months after implantation

Confirmed PT: suspected pump thrombosis in which a thrombus is confirmed in the blood-contacting surfaces of device inflow cannula or outflow conduit or grafts

Secondary outcomes: incidence of suspected or confirmed PT, survival, level of adherence to recommended practices evaluated through 6 months of support

Suspected PT: event in which clinical or mechanical circulatory support device parameters suggest thrombus in the blood-contacting components of the pump, cannulae, or grafts with at least 2 of the 3 following criteria present: hemolysis (clinical hemolysis and/or sustained lactate dehydrogenase > 3 upper laboratory normal limit), worsening heart failure (or lack of left ventricular unloading when a ramp test is performed), abnormal pump parameters (elevated pump powers > 10 W or 2 W higher than baseline)

Baseline Characteristics


HeartMate II patients (N= 300)

Age, years

57 ± 13


52 (17%)

Bridge to transplantation

66 (22%)

New York Heart Association functional class IV

258 (86%)

Interagency Registry for Mechanically Assisted Circulatory Support profiles

Profile 1

Profile 2

Profile 3

Profile 4-7 

38 (13%)

90 (30%)

121 (40%)

51 (17%)

Presence of thrombus

Left atrial thrombus

Left ventricular thrombus

4 (1.3%)

14 (5%)

Left ventricle ejection fraction, %

18 ± 6

Presence of hypercoagulable disorder

46 (15%)

History of valve procedures

20 (7%)



HeartMate II patients (N= 300)

Confirmed PT at 3 months

(N= 307)

9 (2.9%)

Confirmed PT at 6 months

(N= 314)

15 (4.8%)

Suspected PT at 6 months

(N= 314)

20 (6.4%)

Survival at 6 months

Overall survival

Survival free of PT

89% ± 2

84% ± 2

Site adherence to heparin bridging PREVENT recommendations

> 80%

< 80%

(N= 23)

21 (91%)

2 (9%)

Anticoagulant therapy 

Bridged with heparin to warfarin 

Ancoagulated with warfarin 

Median INR (interquartile range [IQR])

Median time spent in the recommended target range of 2 to 2.5 (IQR)




2.1 (1.9 to 2.3)

31% (19 to 44%)

At 3 months, a total of 307 devices were implanted in 300 patients. At 6 months, a total of 314 devices were implanted in 300 patients. A total of 23 sites were included in the study.

The authors reported the composite incidence of suspected thrombosis, hemolysis, or ischemic stroke was significantly lower in patients with good adherence to PREVENT recommendations compared to patients with partial adherence at 6 months (5.7% vs 17.7%, p < 0.01; odds ratio [OR] 3.6; 95% confidence interval [CI] 1.6 to 8). Additionally, the rate of PT was significantly lower in patients whom 100% of the surgical recommendations were adopted, heparin was used to bridge to warfarin with the use of warfarin anticoagulation, and pump speed was ≥ 9,000 rotations per minute compared to patients in whom recommendations were partially adhered to at 6 months (1.9% vs 8.9%, p < 0.01; OR 5.0; 95% CI 1.4 to 18.3).

Adverse Events

Common adverse events at 6 months after implantation: bleeding requiring surgery (16%), early bleeding ≤ 30 days (34%), gastrointestinal bleeding (21%), right heart failure (16%), infection (28%), hemolysis (6.7%)

Serious adverse events at 6 months after implantation: ischemic stroke (4%), hemorrhagic stroke (2.7%)

Percentage that Discontinued due to Adverse Events: N/A

Study Author Conclusions

A structured surgical implant and subsequent clinical management practice pathway is feasible in most patients, and adherence to those recommendations is associated with a low incidence of early PT with HMII.

InpharmD Researcher Critique

The multicenter nature of the study introduces variation in practices among the different institutions making it difficult to evaluate the benefits of PREVENT recommendations in LVAD patients. Additionally, the lack of a control group limits any statistical significance of the results. Overall, this study shows potential anticoagulation practices for LVAD patients.


Maltais S, Kilic A, Nathan S, et al. PREVENtion of HeartMate II pump thrombosis through clinical management: The PREVENT multi-center study. J Heart Lung Transplant. 2017;36(1):1-12. doi: 10.1016/j.healun.2016.10.001


Increased Thromboembolic Events With Dabigatran Compared With Vitamin K Antagonism in Left Ventricular Assist Device Patients


Prospective, randomized, open-label, single-center study

N= 16 (30 was planned)


To assess safety and tolerability of dabigatran etexilate in stable patients after left-ventricular assisted device (LVAD) implantation

Study Groups

Dabigatran (n= 8)

Phenprocoumon (n= 8)

Inclusion Criteria

LVAD implantation > 1 month ago, stable renal function, age > 18 years.

Exclusion Criteria

Severe chronic renal impairment (CrCl < 30 mL/min), history of major thromboembolic or bleeding event, significant bleeding disorder, HIV or hepatitis C infection, heparin-induced thrombocytopenia, hypersensitivity to dabigatran or phenprocoumon.


Patients received the LVAD implant via a minimally invasive approach or full sternotomy. Postoperative anticoagulation consisted of low-molecular-weight heparin which was changed to phenprocoumon afterward. Antithrombotic therapy was added with acetylsalicylic acid 200 mg/day.

Upon randomization into study, patients randomized into the dabigatran group were switched while the control group continued phenprocoumon. Dabigatran was dosed at 110 mg BID for those with normal renal function and 75 mg BID for those with impaired renal function (CrCl > 30 to < 80 mL/min). Phenprocoumon was self-adjusted to meet an INR goal between 2 to 2.5.


Follow-up: Up to 1 year

Outcome Measures

Thromboembolic complication and transplantation

Median time to treatment termination

Baseline Characteristics


Dabigatran (n= 8)

Phenprocoumon (n= 8)


Age, years

61 ± 6 64 ± 9  


0/8 1/7  

Body mass index, kg/m2

27.9 ± 3.1 26.7 ± 3.1  


level 1

level 2

level 3

level 4-6



3 (37.5%)

3 (37.5%)

2 (25%)


5 (62.5%)

2 (25%)


1 (12.5%)


Ischemic cardiomyopathy

3 (37.5%) 5 (62.5%)  

Dilative cardiomyopathy

5 (62.5%) 3 (37.5%)  

Ejection fraction

15.4% ± 4.2% 11.9% ± 4.6%  

Previous smoker

Diabetes mellitus


6 (7.5%)

3 (37.5%)

5 (62.5%)

4 (50%)

1 (12.5%)

5 (62.5%)




Dabigatran (n= 8)

Phenprocoumon (n= 8)


Thromboembolic complication*







Median time to treatment termination, months




*Three pump thrombosis and 1 transient ischemic attack in the dabigatran group. No patients died during observation period.

Study Author Conclusions

Thromboembolic events on dabigatran led to early termination of a randomized controlled trial of dabigatran versus phenprocoumon in left ventricular assist device patients.

InpharmD Researcher Critique

Studies that were halted due to unacceptable risks observed in the treatment group are typically regarded as serious events from the author's perspective. The doses for dabigatran align with guidelines released around 2010 for atrial fibrillation and deep vein thrombosis which may not reflect current practice. Appropriate testing and monitoring of dabigatran through ecarin-based assay or dilute thrombin clotting time assay have not been adopted yet when the study was initiated, meaning that the dose remained consistent with adjusting according to laboratory parameters. It might be possible that with increased monitoring, these events could have been reduced or avoided in the dabigatran group.


Andreas M, Moayedifar R, Wieselthaler G, et al. Increased thromboembolic events with dabigatran compared with vitamin K antagonism in left ventricular assist device patients: a randomized controlled pilot trial. Circ Heart Fail. 2017;10(5):e003709. doi:10.1161/CIRCHEARTFAILURE.116.003709


Factor Xa Inhibitors in Patients with Continuous-Flow Left Ventricular Assist Devices


Retrospective, single-center study

N= 7


To evaluate treatment safety and effectiveness in continuous-flow left ventricular assist device (CF-LVAD) patients who switched from warfarin to a factor Xa inhibitor (apixaban or rivaroxaban) after warfarin failure

Study Groups

All (N= 7)

Inclusion Criteria

Consecutive adults supported by either a HeartMate II (Thoratec Corporation, Pleasanton, CA) or HeartWare (Medtronic, Fridley, MN) CF-LVAD as destination therapy who initially received warfarin anticoagulation therapy and were subsequently switched to a factor Xa inhibitor (apixaban or rivaroxaban) after warfarin therapy failed, as part of their ongoing clinical treatment.

Exclusion Criteria

Mechanical valves or right ventricular assist devices


Patients with renal insufficiency and a lower glomerular filtration rate were switched to apixaban, at the current standard dose of 5 mg twice a day. Patients switched to rivaroxaban received 15 mg once a day, lower than the standard 20 mg/day typically given for stroke prevention in atrial fibrillation due to a history of intracranial hemorrhage indicating increased risk for bleeding.


Trial: Between 2008 and 2018

Outcome Measures

Complication rates (e.g., thrombotic and bleeding events)

Baseline Characteristics

  All (N= 7)      




Age, years


Body mass index, kg/m2



5 (71.42%)            

On warfarin, days

778 ± 689             

Therapeutic INR (2.0-3.0) range while on warfarin, %


Mean INR while on warfarin


On apixaban or rivaroxabn, days

208 ± 157            


Incidence of thrombotic and bleeding events during treatment with warfarin 



Heart failure cause

Type of CF-LVAD

Time under CF-LVAD support, days

Time on warfarin, days  Time within therapeutic INR range, % Reason for change to DOAC (INR value at their of event) 


M Nonischemic HeartMate II 1,788 1,670  28 

Multiple pump thromboses (2.7, 3.4) and noncompliance


M Ischemic HeartWare  1,551 1,187  30 

Stroke (1.4) and GI bleeding (1.3, 2.2, 2.0)

3 M Ischemic  HeartWare  794  413  60 

Stroke (1.9) and ICH (3.1)

4 F Nonischemic HeartWare   318  224  11 

Genetic resistance to warfarin

5 M Ischemic   HeartWare   294  238  22 

Noncompliance with INR checkups

6 M Ischemic  HeartWare   209  163  50 

Supratherapeutic INR and multiple thrombotic events (2.7, 4.6)

7 F Nonischemic HeartWare   1,968  73 

Stroke (1.3), ICH (4.2), and other supratherapeutic INR issues

Incidence of thrombotic and bleeding events during treatment with DOACs

Patient  Time under CF-LVAD support, days Time on DOAC, days DOAC

Major events during DOAC therapy

1,788 105 Rivaroxaban -      
1,551  361  Apixaban Major GI bleeding       
794  381  Rivaroxaban      
4 318  87  Apixaban       
5 294  38  Apixaban      
6 209  105  Apixaban       
7 1,968  382  Rivaroxaban Major GI bleeding       

CF-LVAD continuous-fow left ventricular assist device, DOAC direct oral anticoagulant, F female, GI gastrointestinal, ICH intracranial hemorrhage, INR international normalized ratio, M male

Adverse Events

See "Results"

Study Author Conclusions

Factor Xa inhibitors may be viable treatment options for CF-LVAD patients for whom warfarin therapy has failed. Large prospective studies are necessary to confirm these results.

InpharmD Researcher Critique

The study is limited by its small sample size and the short duration that patients were exposed to apixaban or rivaroxaban as compared to warfarin therapy. The sample size is based on a convenience sample, with no power calculation and only included patients who have failed prior warfarin therapy.  


Parikh VY, Parikh UM, Moctezuma-Ramirez A, et al. Factor Xa inhibitors in patients with continuous-flow left ventricular assist devices. Gen Thorac Cardiovasc Surg. 2020;68(11):1278-1284. doi: 10.1007/s11748-020-01371-w


Anticoagulation with Apixaban in a Patient with a Left Ventricular Assist Device and Gastrointestinal Bleeding: A Viable Alternative to Warfarin?


Case report

Case Presentation

A 78-year-old man reported with refractory ischemic heart failure. His past medical history included coronary artery bypass grafting 18 years prior, and percutaneous coronary intervention with stenting four years prior. Five months prior, the patient experienced lower gastrointestinal bleeding while on dual antiplatelet therapy with aspirin 100 mg daily and clopidogrel 75 mg daily which he was taking as secondary prevention due to acute coronary syndrome.  

Patient received successful implantation of HeartMate II with placement of the inflow cannula in the left ventricular apex with the outflow cannula anastomosed to the ascending aorta. On postoperative day 22, the patient required a blood transfusion as a result of gastrointestinal bleeding and subsequent decrease in hemoglobin. Patient was receiving unfractionated heparin (partial thromboplastin time 50 seconds, INR 1.23) - warfarin had not yet been initiated. Dianostic evaluation eventually revealed multiple angiodysplastic lesions in upper gastrointestinal tract which were treated with argon plasma coagulation; no source for active bleeding was discovered. Anticoagulation therapy was initiated with a target INR of 1.5 to 2.0. 

Patient was discarged after 1.8 months, but returned to hospital five times over the next nine months for upper and lower gastrointestinal bleeding with INR range of 1.23 to 2.29. Warfarin was withheld at each bleeding event and patient was given low-molecular-weight heparin. Due to high risk of bleeding, patient was initiated on regimen of apixaban 2.5 mg twice daily. Over the following year, no further episodes of bleeding occurred, and the patient reported no signs or symptoms of left-ventricular assist device (LVAD) thrombosis. 

Study Author's Conclusions

This is the first report in the literature that describes the use of anticoagulation therapy with apixaban in a patient receiving LVAD support with recurrent gastrointestinal bleeding and warfarin intolerance. The patient was treated as an outpatient with apixaban for 1 year, and to date there have been no signs of device thrombosis. 




Pollari F, Fischlein T, Fittkau M, et al. Anticoagulation with apixaban in a patient with a left ventricular assist device and gastrointestinal bleeding: A viable alternative to warfarin? J Thorac Cardiovasc Surg. 2016;151(4):e79-81. doi:10.1016/j.jtcvs.2015.10.059


Dabigatran Etexilate in a Vitamin-K Antagonist Non-Responder Patient During Heartware HVAD Support


Case report

Case Presentation

A 70-year-old female with dilated cardiomyopathy received continuous-flow left ventricular assist device (LVAD) implantation with postoperative anticoagulation beginning 24 hours after using sodium heparin. On the third postoperative day, the patient received warfarin (therapeutic range 1.8 to 2.5) and aspirin 300 mg/day with no major complications at discharge.

Three months later, the patient was hospitalized for low INR (1.33) despite warfarin doses up to 7.5 mg/day. The patient weighed 42 kg. The dose of warfarin was increased up to 17.5 mg/day with no success and was decided to replace it with sintrom (up to 16 mg/day) with LMWH (nadroparin calcium, 3,800 UI x 2/day). After ten days of therapy, the INR remained unresponsive (1.05).

After a month of LMWH 7,600 UI/day, the patient developed ischemic stroke with right hemiplegia and motor aphasia. Platelet inhibition was observed with aspirin 150 mg/day. LMWH was discontinued for dabigatran 300 mg/day (150 mg BID) and after 7 days of monitoring, the patient was discharged. Prior to discharge, the patient observed prolonged thrombin time, INR 1.50, aPTT 140.3 sec, and aPTT ratio of 4.13. The reason for warfarin resistance was not investigated. Subsequent follow up observed recovery of cardiac function (ejection fraction of last exam 50% to 55%) with one complication due to a driveline infection. The LVAD was removed after 397 days of dabigatran therapy with no reports of ischemic or bleeding events.

Study Authors' Conclusions

In our patient, the use of dabigatran was necessary because of the inability to anticoagulant the patient with warfarin and sintrom. However, because of the increased rates of thrombotic events with mechanical valves, it will be necessary to monitor the use of dabigatran in a larger series of LVAD patients before the efficacy and safety of this anticoagulant can be determined in these patients.




Baronetto A, Centofanti P, Attisani M, et al. Dabigatran etexilate in a vitamin-K antagonist non responder patient during Heartware HVAD support. J Card Surg. 2017;32(2):166-167. doi: 10.1111/jocs.13097.


Anticoagulation Therapy for a LVAD Patient With Acquired Warfarin Resistance


Case Report

Case Presentation

A 30-year-old man with a history of end-stage idiopathic dilated cardiomyopathy was referred to the hospital for LVAD and heart transplant therapy. After enrollment in the national heart transplantation list, the patient received a third-generation centrifugal DuraHeart (Terumo, Japan) LVAD implantation. The patient was initiated on Aspirin 100 mg daily, warfarin 2 mg daily, and continuous intravenous heparin. Within the first week of LVAD implantation, a target INR of 2.0 – 2.3 was achieved with warfarin 3 mg daily. Three months after implantation, the patient was discharged without any complications.

Approximately six months post-implantation, he was re-admitted for evaluation of native heart recovery which failed to show adequate recovery. Additionally, his INR decreased from 1.2 to 1.4 with no regard to changes in warfarin dose. Despite this decrease, it was confirmed that the patient was adherent to therapy and dietary restrictions. As a result, his warfarin dose was increased gradually. After maxing out his recommended warfarin dose, his INR remained below 1.5, requiring him to be initiated on a continuous heparin infusion. Additionally, bucolome, an agent that reduces warfarin protein-binding rate, was administered however, the INR therapeutic range was not achieved. After further investigation of his warfarin blood concentrations, it was determined that he may have malabsorption of warfarin for an unclear reason.

After being on heparin for one month, the patient and family gave consent for the off-label use of dabigatran, an oral direct thrombin inhibitor. The patient was initiated on a new anticoagulation regimen consisting of 10 mg of oral warfarin, 600 mg of bucolome, and 150 mg of dabigatran twice daily. After discharge, his INR remained between 1.2 and 1.5, showing no signs of thromboembolic events. After two months, he developed left-sided hemiplegia and disruption of the right middle cerebral artery was noted. He had an emergency thrombectomy and showed complete neurological recovery after 1 month.

Post cerebrovascular event, dabigatran was discontinued, and the patient was reinitiated on heparin infusion and warfarin 5 mg daily. With this regimen, he had to stay at the hospital for 2 years while waiting for heart transplantation. During this time, he had frequent bacteremia due to a peripheral intravenous line.

Study Authors' Conclusions

Anticoagulation therapy for patients with a medical device is mandatory in postoperative management. Despite sufficient anticoagulation therapy, thromboembolic events can still occur. This remains an ongoing concern for patients with LVAD.

To the authors’ knowledge, this is the first case of a patient with LVAD showing warfarin resistance. Safety and efficacy regarding anticoagulation with factor Xa-inhibitors for LVAD patients remains unclear. However, the management of anticoagulation with heparin is essential in these patients.



Yoshioka D, Toda K, Hidaka T, et al. Anticoagulation therapy for a LVAD patient with acquired warfarin resistance. J Artif Organs. 2017;20(3):260-262. doi:10.1007/s10047-017-0947-8