A FRAMEWORK FOR PRACTICE ON PERI-OPERATIVE PATIENT BLOOD MANAGEMENT AND ANTI-COAGULATION IN KIDNEY TRANSPLANTATION

2.5. Strategies to prevent thrombosis post kidney transplantation

Given the type of procedure and associated risk of VTE, in line with the NICE 2018 guidelines, kidney transplant recipients should be offered VTE prophylaxis, which includes(1):

1. General measures
2. Mechanical methods.
3. Pharmacological methods: Consideration of pharmacological VTE prophylaxis for a minimum of 7 days, where risk of VTE outweighs risks of bleeding. The competing risk of bleeding versus thrombosis requires regular review and re-assessment at all stages; pre-, peri- and post- transplantation.

NICE no longer recommends the use of unfractionated heparin (UFH) as first line VTE prophylaxis but rather low molecular weight heparin (LMWH).  There is insufficient evidence to make a specific recommendation of one over the other in the setting of kidney transplantation, however individual patient factors and centre specific practices may influence choice of agent.

Since the publication of the last NICE guidelines on VTE prophylaxis, The Graduated compression stockings as Adjuvant to Pharmaco-thromboprophylaxis in elective Surgical patients (GAPS) study has suggested that the administration of pharmaco-thromboprophylaxis alone is non-inferior to a combination of pharmaco-thromboprophylaxis and GECS. The study investigators concluded that in patients receiving LMWH prophylaxis, additional use of GECS may be unnecessary(2). This important study is likely to change national guidance on the approach to VTE prophylaxis and can be considered in the management of VTE prophylaxis in kidney transplant recipients(2, 3).

2.5.1. General Measures

• All kidney transplant recipients should be mobilised early and have leg exercises encouraged to prevent VTE(1). (1A)
• All kidney transplant recipients should undergo regular fluid assessment to optimise intravascular volume to reduce the risk of VTE(1). (1C)

 

Rationale:

1. Mobilisation and Leg exercises
   The estimated reported incidence of DVT in kidney transplant recipients is 7%(4).  Immobility increases the risk of DVT (Deep Vein Thrombosis) around 10-fold. Early mobilisation and leg exercises should be encouraged in all patients.
2. Hydration
   Dehydration leading to haemoconcentration increases blood viscosity and reduces blood flow. Adequate hydration should be ensured in immobilised patients. Many patients going into kidney transplantation have a degree of salt and fluid overload; post-transplant, in early post operative period, some patients develop polyuria (UO of >3L/day) leading to significant fluid shifts and resultant haematological changes. Careful clinical assessments and patient specific fluid prescriptions are recommended to optimise intravascular fluid volumes to reduce the risk of venous thromboembolism whilst minimising the risk of fluid overload.

References

1. National Institute for Health and Care Excellence. Venous thromboembolism in over 16s: reducing the risk of hosptial-acquired deep vein thrombosis or pulmonary embolism [N89]. 2018.
2. Shalhoub J, Lawton R, et al. Graduated compression stockings as adjuvant to pharmaco-thromboprophylaxis in elective surgical patients (GAPS study): randomised controlled trial. BMJ. 2020;369:m1309.
3. Turner BRH, Machin M, et al. An Updated Systematic Review and Meta-analysis of the Impact of Graduated Compression Stockings in Addition to Pharmacological Thromboprophylaxis for Prevention of Venous Thromboembolism in Surgical Inpatients. Annals of surgery. 2024;279(1):29-36.
4. Verhave JC, Tagalakis V, et al. The risk of thromboembolic events in kidney transplant patients. Kidney international. 2014;85(6):1454-60.

 

2.5.2. Mechanical Methods

• All patients should be offered Graduated Elastic Compression Stockings (GECS) on admission for a kidney transplant, provided there is no contraindication(1). (1A)
• All patients not receiving pharmacological prophylaxis post-operatively should be encouraged to wear GECS day and night until they no longer have significantly reduced mobility(1). (1A)
• Intermittent Pneumatic Compression (IPC) may be used as an alternative to GECS (1) (1A)

 

Rationale:

Unlike pharmacological methods, mechanical methods do not increase the risk of bleeding and may be preferred in patients in whom the risk of bleeding may outweigh the antithrombotic efficacy of pharmacological prophylaxis.  However, it needs to be considered that a significant proportion of kidney transplant recipients may have a relative or absolute contraindication to GECS or IPC.

2.5.2.1. Graduated compression stockings:

Graduated Elastic Compression Stockings (GECS) are recommended for all grades of DVT risk in surgical patients. GECS should be applied pre-operatively following a formal assessment of the contraindications. General guidance suggests that GECS alone effect a three-fold reduction in the risk of DVT. Above knee GECS are more effective than below-knee GECS for prophylaxis of DVT.

GECS are contraindicated in patients with:

• suspected or proven peripheral arterial disease, or previous peripheral arterial bypass grafting
• peripheral neuropathy or other causes of sensory impairment
• any local conditions in which anti-embolism stockings may cause damage – for example, fragile ’tissue paper’ skin, dermatitis, gangrene or recent skin graft
• known allergy to material of manufacture
• severe leg oedema
• major limb deformity or unusual leg size or shape preventing correct fit.

Care must be taken to provide the correct size to patients and demonstrate the correct way to wear them. Patients should be encouraged to wear them day and night until they no longer have significantly reduced mobility.

2.5.2.2. Intermittent Pneumatic Compression

IPC devices are a method of prophylaxis that includes an air pump and inflatable garments in a system designed to improve venous circulation in the lower limbs of people at risk of DVT or pulmonary embolism. The inflation–deflation cycle of intermittent pneumatic compression therapy simulates the thigh, calf and foot’s normal ambulatory pump action increasing both the volume and rate of blood flow, eliminating venous stasis and replicating the effects of the natural muscle pump. Intermittent pneumatic compression devices can be thigh- or knee-length sleeves that are wrapped around the leg, or a garment that can be wrapped around or worn on the foot that is designed to mimic the actions of walking. Used alone they appear to reduce risk of asymptomatic DVT by 50%.

Similar to GECS they are contraindicated in patients with:

• Significant peripheral vascular disease.
• Any local conditions in which anti-embolism stockings may cause damage – for example, fragile ’tissue paper’ skin, dermatitis, gangrene or recent skin graft
• Marked leg oedema.
• Marked limb deformity.
• Pre-existing DVT.

 

Combined modality treatment

There is interest in whether combined modalities such as GECS in combination with IPC devices can further reduce the risk of post operative venous thrombosis especially in patients ineligible for pharmacological prophylaxis. A systematic review in 2022 concluded that whilst there was a lack of evidence comparing combination therapy with IPCs alone, this strategy may be advantageous in high-risk patients(2).

Audit and Research Recommendations

Audit:  Proportion of kidney transplant recipients with a relative contraindication to the use of GECS or IPC. 

Research: Given data from the GAPS study, patient reported measures/acceptability on the use of GECS or IPC may influence patient management.

Research: Comparison of pharmacological alone or combination of mechanical and pharmacological VTE prophylaxis in kidney transplant recipients.

 

References

1. National Institute for Health and Care Excellence. Venous thromboembolism in over 16s: reducing the risk of hosptial-acquired deep vein thrombosis or pulmonary embolism [N89]. 2018.
2. Herring B, Lowen D, et al. A systematic review of venous thromboembolism mechanical prophylaxis devices during surgery. Langenbeck’s archives of surgery. 2023;408(1):410.

 

2.5.3. Pharmacological Prophylaxis and monitoring

• We recommend kidney transplant recipients be assessed for pharmacological venous thrombosis prophylaxis where the risk of VTE outweighs risk of bleeding for a minimum of 7 days post-transplant(1). (1C)
• Either unfractionated heparin or low molecular weight heparin may be used for prophylaxis for venous thromboembolism in kidney transplant recipients(2) (2D)

 

Rationale:

NICE currently recommends LMWH over UFH for VTE prophylaxis in hospitalised patients,  however for patients with renal impairment either LMWH or UFH may be used, following appropriate dose adjustment(1).  It is important to re-iterate that these recommendations are to prevent DVT/PE and are not to guide management to prevent graft thrombosis.

Recent data from a European survey on anti-coagulation practices suggests that for standard risk patients, LMWH is now more commonly used for VTE prophylaxis in kidney transplantation than UFH(3).  Only one prospective study has investigated the risk of bleeding versus thrombotic events by anti-coagulant therapy post-kidney transplant.  The study investigated ‘low risk living donor recipients’, and randomised 75 patients to receive no anti-coagulation, LMWH or UFH post-transplant.  There were no differences in clinical outcomes between the 3 groups, with only one major bleeding episode occurring in the LMWH group, which was related to a slipped ligature of the inferior epigastric artery(4).

If LMWH is being used for VTE prophylaxis, choice of agent will be dependent upon local availability, and consideration will be needed for the different agents and corresponding doses, weight of patient and renal function.  A systematic review investigating whether prophylactic doses of LMWH accumulated in renal impairment, reported tinzaparin and dalteparin are likely to be safe, whilst enoxaparin did show accumulation in patients with a creatinine clearance of <30mls/min(5). In one retrospective study, therapeutic doses of dalteparin were at least as safe as UFH in patients with eGFRs<30mls/min(6). The British National Formulary recommends that renal function is measured either in terms of eGFR  corrected for body surface area or creatinine clearance as calculated using the Cockcroft-Gault Equation, Creatinine Clearance (Cockcroft-Gault Equation).

In addition to renal function, consideration of body weight and thrombotic risk is required.  With any given fixed dose of LMWH, patients of low body-weight are at increased risk of bleeding, whilst patients of high body-weight index are at increased risk of thromboembolism(7, 8).  A guide for dosing of patients with UFH or LMWH to prevent VTE is shown in Table 7.  Prophylactic therapy should only be started when the responsible teams are satisfied that haemostasis is established, which usually occurs on day 1 post op.

Table 7.  Guide to pharmacological thromboembolic prophylaxis dosing in adult kidney transplant recipients

	Low Risk	High Risk
UFH	2500U twice a day	5000U twice a day
Enoxaparin	20mg once a day*	40mg once a day*
Dalteparin	2500U once a day	5000U once a day
Tinzaparin	2500U-3500U once a day	4500U once a day

*caution with enoxaparin use in patients with a creatinine clearance of <30mls/min, avoid if <15mls/min Whilst the recommendation is that patients are assessed to receive anti-coagulation for 7 days, it is accepted that this timeline may vary e.g. for pragmatic reasons the decision to stop VTE prophylaxis at discharge should this occur before 7 days may occur, whilst conversely patients with prolonged DGF who require admission beyond 7 days, should be considered for prolong use in keeping with hospitalised patients. Monitoring of anti-Xa levels in patients receiving LMWHs

LMWH inhibits coagulation by activating antithrombin III, which binds to and inhibits factor Xa; inactivation of Xa prevents thrombin activation which stops the conversion of fibrinogen to fibrin, and therefore clot formation.  In patients with renal impairment receiving therapeutic doses of LWMH, monitoring of anti-Xa levels is recommend, however monitoring is not considered routine in patients receiving prophylactic doses of LWMH(9). For those receiving treatment dose, anti-Xa levels should be taken between 3-5 hours after the third dose(9).

Monitoring for Heparin induced thrombocytopenia

For patients receiving UFH or LMWH, monitoring of the platelet count for the development of heparin induced thrombocytopenia (HIT) is required for courses lasting longer than 4 days(10).  HIT diagnosis should be considered when platelet count drops >50%, if there is a fall in platelet count of >50% within 24 hours if patients have received heparin in the last 100 days or if there is concurrent thrombosis. It is estimated that the majority of kidney transplant recipients would have received heparin prior to transplantation, but not all, e.g. pre-emptive transplant recipients. If HIT is being considered a 4Ts score should be calculated prior to consideration of screening for HIT(10). The components of the score include presence of thrombocytopenia, timing of platelet count fall post heparin, thrombosis history and the presence or absence of other causes of thrombocytopenia.  Online calculators exist: https://www.mdcalc.com/calc/1787/4ts-score-heparin-induced-thrombocytopenia.

Urgent reversal of unfractionated heparin and LMWH

In the context of bleeding (see section below), stopping prophylactic UFH and LMWH and application of general haemostatic measures is often sufficient to control (stop or prevent) bleeding, and specific anti-dotes are not required. Where therapeutic doses are being used in the context of bleeding, management should involve discussion with haematology, who may advise protamine(11).  The effect of protamine on LWMH activity is less than on UFH but can be considered within 8 hours of LMWH administration [87].

Audit and Research Recommendations

Audit:  Type and duration of VTE use (LMWH/UFH/mechanical) and incidence of thrombosis/bleeding across broad cohorts of kidney transplant recipients.

Research: Use of UFH versus LMWH for pharmacological prophylaxis in kidney transplantation and association with thrombosis or bleeding risk.

 

References

1. National Institute for Health and Care Excellence. Venous thromboembolism in over 16s: reducing the risk of hosptial-acquired deep vein thrombosis or pulmonary embolism [N89]. 2018.
2. UKKA.Anti-coagulation for venous thromboembolism in adults with aaaaadvanced kidney disease (Draft Guidelines). 2025.
3. van den Berg TAJ, Lisman T, et al. Antithrombotic Management in Adult Kidney Transplantation: A European Survey Study. European surgical research Europaische chirurgische Forschung Recherches chirurgicales europeennes. 2023;64(2):169-76.
4. Osman Y, Kamal M, et al. Necessity of routine postoperative heparinization in non-risky live-donor renal transplantation: results of a prospective randomized trial. Urology. 2007;69(4):647-51.
5. Atiq F, van den Bemt PMLA, et al. A systematic review on the accumulation of prophylactic dosages of low-molecular-weight heparins (LMWHs) in patients with renal insufficiency. Eur J Clin Pharmacol. 2015;71(8):921-9.
6. Park D, Southern W, et al. Treatment with Dalteparin is Associated with a Lower Risk of Bleeding Compared to Treatment with Unfractionated Heparin in Patients with Renal Insufficiency. J Gen Intern Med. 2016;31(2):182-7.
7. Knox H, Edwin SB, et al. Venous Thromboembolism Prophylaxis in Low Body Weight Critically Ill Patients. Journal of intensive care medicine. 2024;39(5):493-8.
8. Garcia DA, Baglin TP, et al. Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e24S-e43S.
9. Sikes L, Charles K, et al. Anti-Factor Xa Level Monitoring for Enoxaparin Prophylaxis and Treatment in High-Risk Patient Groups. HCA healthcare journal of medicine. 2023;4(2):105-9.
10. Arachchillage DJ, Thachil J, et al. Diagnosis and management of heparin-induced thrombocytopenia: Third edition. British Journal of Haematology. 2024;204(2):459-75.
11. Makris M, Van Veen JJ, et al. Guideline on the management of bleeding in patients on antithrombotic agents. British Journal of Haematology. 2013;160(1):35-46.

 

 

2.5.3.1. Management of concomitant anti-platelet therapy at the time of kidney transplantation

• Aspirin should be used for secondary cardiovascular prevention in kidney transplant recipients(1). (1A)

 

Rationale

Aspirin is prescribed for many kidney transplant candidates for secondary cardiovascular prevention(2, 3). For patients on anti-platelet therapy at the time of transplant, there is minimal evidence to guide safety of continuation during the peri-operative period.

For patients undergoing general surgical procedures, the British Society of Haematology guidelines on the peri-operative management of anti-coagulation and antiplatelet therapy supports continuation of aspirin if the bleeding risk is considered low(4). However, when considering use of aspirin, it should be noted that evidence suggests that omission of aspirin (up to 7 days post-op) does not increase risk of death or major cardiac adverse events, but aspirin use does increase risk of bleeding in non-cardiac surgery(5). This supports omission of aspirin during the first 7 days post-transplant, in those patients prescribed it pre-transplantation.  However, a recent European survey reported that the majority of transplant professionals do not stop aspirin at the time of transplantation(6). With one retrospective study showing continued use of antiplatelet therapy with prophylactic heparin was not associated with an increased risk of bleeding, with another large retrospective study reporting there was a risk (7, 8). Routine ongoing use of antiplatelet agents needs to be weighed up between practical considerations regarding contribution not only to post-operative bleeding events but also planned interventions (e.g. biopsy), where use of anti-platelet therapy would be undesirable. Although risk of major bleeding is low in patients undergoing native renal biopsies, less data available in transplant recipients, especially in the context of early allograft dysfunction(9-11). It should be noted there is no high-quality evidence that aspirin use reduces risk of renal vein thrombosis in kidney transplant recipients(12).

For patients on dual anti-platelet therapy (DAPT), ideally transplantation should be avoided during a period associated with high thrombotic risk in the absence of DAPT, e.g. following drug eluting stent insertion. When thrombotic risk reduces, transplantation may be considered with aspirin monotherapy(13).  There is limited data on the safety of clopidogrel monotherapy in kidney transplantation(14).

There is also a lack of evidence on the beneficial effects of aspirin (or other anti-platelet therapy) beyond the immediate post-operative period.  A recent large, retrospective, single centre study showed extended use aspirin did not reduce incidence of VTE post-kidney transplantation, which was low(15). However, a recent meta-analysis investigating the effect of aspirin on kidney allograft outcomes suggested a reduced risk of graft failure, thrombosis, major adverse cardiovascular event (MACE) and mortality with its use(16). In addition, the safety profile appears reassuring(16). This meta-analysis included several studies from the UK, all routinely using aspirin between 28 days and 3 months post-transplant(17-20).  In another non-systematic review of aspirin use to prevent cardiac events post-transplant, data suggested that aspirin should be used in those with established cardiovascular disease as secondary prevention, but that there was insufficient data in kidney transplant recipients to recommend its use in primary prevention(21).

Audit and Research Recommendations

Audit: Management of aspirin in kidney transplant recipients and associated outcomes.

Research: Prospective studies on the use of aspirin as primary prevention in the medium to long term in kidney transplant recipients

 

References

1. National Institute for Health and Care Excellence.Anti-platelet treatment for prevention of cardiovascular disease. . 2025.
2. Pallikadavath S, Ashton L, et al. Aspirin for the primary prevention of cardiovascular disease in individuals with chronic kidney disease: a systematic review and meta-analysis. European journal of preventive cardiology. 2022;28(17):1953-60.
3. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney international. 2024;105(4s):S117-s314.
4. Keeling D, Tait RC, et al. Peri-operative management of anticoagulation and antiplatelet therapy. British Journal of Haematology. 2016;175(4):602-13.
5. Devereaux PJ, Mrkobrada M, et al. Aspirin in Patients Undergoing Noncardiac Surgery. New England Journal of Medicine. 2014;370(16):1494-503.
6. van den Berg TAJ, Lisman T, et al. Antithrombotic Management in Adult Kidney Transplantation: A European Survey Study. European surgical research Europaische chirurgische Forschung Recherches chirurgicales europeennes. 2023;64(2):169-76.
7. Hau HM, Eckert M, et al. Predictive Value of HAS-BLED Score Regarding Bleeding Events and Graft Survival following Renal Transplantation. Journal of clinical medicine. 2022;11(14).
8. Ng JC, Leung M, et al. Evaluation of Heparin Anticoagulation Protocols in Post-Renal Transplant Recipients (EHAP-PoRT Study). The Canadian journal of hospital pharmacy. 2016;69(2):114-21.
9. Baffour FI, Hickson LJ, et al. Effects of Aspirin Therapy on Ultrasound-Guided Renal Allograft Biopsy Bleeding Complications. Journal of vascular and interventional radiology : JVIR. 2017;28(2):188-94.
10. Kumar V, Mitchell MD, et al. Risk of complications with use of aspirin during renal biopsy: A systematic review. Clinical nephrology. 2018;89(2):67-76.
11. Lees JS, McQuarrie EP, et al. Risk factors for bleeding complications after nephrologist-performed native renal biopsy. Clinical kidney journal. 2017;10(4):573-7.
12. Surianarayanan V, Hoather TJ, et al. Interventions for preventing thrombosis in solid organ transplant recipients. The Cochrane database of systematic reviews. 2021;3(3):Cd011557.
13. Savonitto S, Caracciolo M, et al. Management of patients with recently implanted coronary stents on dual antiplatelet therapy who need to undergo major surgery. Journal of thrombosis and haemostasis : JTH. 2011;9(11):2133-42.
14. Benahmed A, Kianda M, et al. Ticlopidine and clopidogrel, sometimes combined with aspirin, only minimally increase the surgical risk in renal transplantation: a case-control study. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association – European Renal Association. 2014;29(2):463-6.
15. Pegler AH, Hegerty K, et al. Incidence of Thromboembolic Complications Following Kidney Transplantation with Short and Extended Aspirin Prophylaxis: A Retrospective Single-Center Study. Ann Transplant. 2023;28:e939143.
16. Cheungpasitporn W, Thongprayoon C, et al. The effect of aspirin on kidney allograft outcomes; a short review to current studies. Journal of nephropathology. 2017;6(3):110-7.
17. Murphy GJ, Taha R, et al. Influence of aspirin on early allograft thrombosis and chronic allograft nephropathy following renal transplantation. The British journal of surgery. 2001;88(2):261-6.
18. Robertson AJ, Nargund V, et al. Low dose aspirin as prophylaxis against renal-vein thrombosis in renal-transplant recipients. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association – European Renal Association. 2000;15(11):1865-8.
19. Stechman MJ, Charlwood N, et al. Administration of 75 mg of aspirin daily for 28 days is sufficient prophylaxis against renal transplant vein thrombosis. Phlebology. 2007;22(2):83-5.
20. Taha R, White SA, et al. Antithrombotic effects of aspirin after renal transplantation. Transplant Proc. 2000;32(3):550.
21. Khalil MAM, Khalil M, et al. Pros and Cons of Aspirin Prophylaxis for Prevention of Cardiovascular Events in Kidney Transplantation and Review of Evidence. Advances in preventive medicine. 2019;2019:6139253.

 

2.5.3.2. Management of concomitant oral anti-coagulation therapy at the time of kidney transplantation

 

We recommend the management of patients receiving oral anticoagulation should be undertaken as set out below:

• Transplantation should be deferred for 3-months following an acute thrombotic event (1). (1C)
• Patients at high thrombotic risk on long term anti-coagulation should have an anti-coagulation plan is made in advance of transplantation with a haematologist(1). (1C)
• Transplant candidates on the deceased donor wait-list requiring long term anti-coagulation, should have warfarin in preference to direct-acting oral anticoagulation, to enable rapid reversibility(2). (1C)
• For patients receiving warfarin therapy at the time of deceased donor transplantation, effective reversal will include the use of vitamin K and/or prothrombin complex concentrate depending on INR and whether timing of surgery is planned for <6-8 hours(1). Cases should be discussed with the local haematology team. (1B)

 

Rationale:

Warfarin

All patients should have the indication and treatment duration for warfarin clearly identified at the time of starting therapy or wait list activation. It is recommended that transplantation is deferred for 3-months following a thrombotic event e.g. VTE or stroke/TIA. Patients outside a 3-month thrombotic event window, may be considered high risk of a peri-operative thrombotic event as outlined in Table 3.

Most surgeons would require an INR<1.5 (some <1.3) for a kidney transplant to proceed. Transplantation from living donors in patients receiving warfarin at low risk of thrombotic event

For patients undergoing elective LD transplantation, the following approach may be applied(3):

• Withold warfarin for 5 days prior to the procedure
• Check the INR on the day prior to the procedure:

If INR ≤1.5 – proceed

If INR 1.6-1.7 – administer 1 mg oral/IV vitamin K

If INR 1.8 or more – administer 2 mg- 5mg vitamin K and seek haematology advice

• Repeat INR on day of procedure to ensure INR <1.5

Transplantation from deceased donors in patients receiving warfarin at low risk of thrombotic event

If time to deceased donor transplantation is >6-8 hours, 5mg of IV vitamin K may be given, and recheck INR after 6 hours. Where transplantation is taking place in <6 hours, warfarin can be reversed with 25–50 u/kg of four-factor prothrombin complex concentrate. Vitamin K should also be given concurrently and the INR rechecked after 30 minutes to ensure if it safe to proceed (1). Transplantation in patients receiving warfarin at high risk of a thrombotic event

These patients may need additional ‘bridging’ therapy with therapeutic doses of heparin (LMWH or UFH) whilst the INR is not in target range(1). It is recommended that high risk patients have an anti-coagulation plan made with haematology prior to transplantation, with individualised plans made according to clinical indications and nature of surgery (elective living or emergency deceased donor).

Timing of re-initiation of anti-coagulation post-surgery will depend upon clinical course, with bridging requirement dependent on indication.

Direct-Acting Oral Anticoagulants

Whilst there are an increasing number of reports on the safety profile of DOACs in patients with end stage kidney failure, it is not recommended that patients on the deceased donor wait list are maintained on DOACs due to the need to reverse the agents urgently, should a recipient be offered an organ. Patients with a planned living donor however may be maintained on a DOAC, with the recommended wash out period being 72 hours(1).  A reversal agent Andexanet alpha is available for reversal of DOACs in the situation of life-threatening haemorrhage. There is scare data available on the use of Andexanet for reversal of apixaban, rivaroxaban or edoxaban in the pre-operative phase. Use of Andexanet prior to surgery is associated with temporary heparin resistance(4).

 

Audit and Research Recommendations

Audit: Prevalence and outcomes of transplant recipients receiving long term oral anti-coagulation agents at the time of transplant.

Audit: Comparison of outcomes with recipients receiving bridging with LMWH or UFH.

References

1. Keeling D, Tait RC, et al. Peri-operative management of anticoagulation and antiplatelet therapy. British Journal of Haematology. 2016;175(4):602-13.
2. Saja K, Haemostasis, et al. Addendum to the guideline on the peri-operative management of anti-coagulation and anti-platelet therapy. British Journal of Haematology. 2022;197(2):188-9.
3. Keeling D, Baglin T, et al. Guidelines on oral anticoagulation with warfarin – fourth edition. British Journal of Haematology. 2011;154(3):311-24.
4. Dohle D-S, Pfeiffer P, et al. Andexanet alfa and heparin resistance in cardiac surgery: Experiences and risks associated with the reversal of direct oral anticoagulants. European Journal of Cardio-Thoracic Surgery. 2023;63(6).

 

2.5.4.  Use of viscoelastic testing in kidney transplantation

• We do not recommend the routine use of viscoelastic testing in kidney transplantation. (1D)

Rationale

Viscoelastic testing, using thromboelastography (TEG) or rotational thromboelastometry (ROTEM) has been used to assess coagulation of whole blood in the fields of trauma, cardiac surgery and liver transplantation(1, 2).  Viscoelastic testing evaluates clot formation, clot propagation and clot lysis (or fibrinolysis).  The kit uses <0.5ml of blood, and the instrument generates a curve, depicting each of the steps from clot formation to lysis, which informs coagulation status. As a point of care test it may rapidly inform an individual patients coagulation needs in cardiac surgery and liver transplantation, and as such, has widening areas of potential application(3).  The use of viscoelastic testing in guiding anti-coagulation needs in pancreas transplantation has been studied in two retrospective studies(4, 5). Whilst viscoelastic assessments have been shown to predict renal transplant outcome in terms of graft function in one study, the benefit of routine viscoelastic assessments in the kidney transplantation to help to inform individualised patient coagulation needs is not known(6). However, it may be considered useful in individual cases, where risk of bleeding is high, or where bleeding complications occur intra-operatively. Audit and Research Recommendations

Audit: Use of viscoelastic testing in kidney transplant recipients where risk of bleeding high or bleeding occurs intra-operatively.

 

References

1. Hartmann J, Hermelin D, et al. Viscoelastic testing: an illustrated review of technology and clinical applications. Research and practice in thrombosis and haemostasis. 2023;7(1):100031.
2. Wikkelsø A, Wetterslev J, et al. Thromboelastography (TEG) or thromboelastometry (ROTEM) to monitor haemostatic treatment versus usual care in adults or children with bleeding. The Cochrane database of systematic reviews. 2016;2016(8):Cd007871.
3. National Institute for Health and Care Excellence.Detecting, managing and monitoring haemostasis: viscoelastometric point-of-care testing (ROTEM, TEG and Sonoclot systems). 2014.
4. Vaidya A, Muthusamy AS, et al. Simultaneous pancreas–kidney transplantation: to anticoagulate or not? Is that a question? Clin Transplant. 2007;21(4):554-7.
5. Gopal JP, Dor FJ, et al. Anticoagulation in simultaneous pancreas kidney transplantation – On what basis? World journal of transplantation. 2020;10(7):206-14.
6. Walker CB, Moore HB, et al. The use of thromboelastography to assess post-operative changes in coagulation and predict graft function in renal transplantation. American journal of surgery. 2020;220(6):1511-7.

 

2.5.5.  Intraoperative haemostasis considerations

• The use of intra-operative anti-coagulation and haemostatic agents should be individualised to risk of thrombosis or bleeding, with no recommendation for routine use in all patients. (2C)

Use of either intra-operative anti-coagulation or haemostatic agents should be individualised to the risk of thrombosis or bleeding respectively (outlined elsewhere), and will vary according to preference of operating surgeon.  Meticulous surgical technique remains the cornerstone in the prevention against complications, and there are no recommendations for routine use of either anti-coagulation or haemostatic agents. However, evidence and safety of interventions are outlined below:

1. Intra-operative use of anti-coagulation
   Whilst the use of intra-operative of unfractionated heparin is common in vascular procedures, data on the use in the setting of kidney transplantation is limited(1-4).  Reassuringly, the use of intraoperative intravenous heparin has not been shown to be associated with increased haemorrhagic complications, in three retrospective cohort studies(1-3).  Although, its use was neither associated with a significant reduction in graft thrombosis when investigated in one study(2).
2. Intra-operative use of haemostatic agents
   Intraoperative haemostasis is most commonly managed with the use of sutures or electrocautery(5). Topical haemostatic agents may support control of bleeding(5).  A few studies have reported the use of the various different agents in the setting of kidney transplantation.  One prospective RCT, randomised 30 patients to receive a polyethylene glycol (PEG)-coated collagen patch (Hemopatch^®) or standard of care (electrocautery or clips), and showed that the patch was safe with comparable clinical outcomes of estimated blood loss(6). Whilst a further prospective study, assessed the use of an absorbable polysaccharide hemostatic powder (HaemoCer™) in 147 patients, and found compared with a historical control group, lymphocele development was significantly reduced(7).  Further retrospective studies of the use of haemostatic biomaterials have been reported suggesting the agents are safe, and in one study, that the use of a fibrin sealant at the venous anastomosis in 82 patients, and found its use was also associated with a reduction in blood loss(8, 9).  There is no data to inform optimal use of these agents in kidney transplantation, related to type of agent and indication, which should be the focus of future research.

Audit and Research Recommendations

Audit: Prevalence (indications and patient characteristics) for the intra-operative use of haemostatic agents in kidney transplant recipients and outcomes.

 

References

1. van den Berg TAJ, Minnee RC, et al. Perioperative antithrombotic therapy does not increase the incidence of early postoperative thromboembolic complications and bleeding in kidney transplantation – a retrospective study. Transpl Int. 2019;32(4):418-30.
2. Denize J, Defortescu G, et al. Is intraoperative heparin during renal transplantation useful to reduce graft vascular thrombosis? Progrès en Urologie. 2021;31(8):531-8.
3. Mohan P, Murphy DM, et al. THE ROLE OF INTRAOPERATIVE HEPARIN IN CYCLOSPORINE TREATED CADAVERIC RENAL TRANSPLANT RECIPIENTS. The Journal of Urology. 1999;162(3, Part 1):682-4.
4. van den Berg TAJ, Nieuwenhuijs-Moeke GJ, et al. Pathophysiological Changes in the Hemostatic System and Antithrombotic Management in Kidney Transplant Recipients. Transplantation. 2023;107(6):1248-57.
5. Brown KGM, Solomon MJ. Topical haemostatic agents in surgery. BJS. 2023;111(1).
6. Kapoor A, Wong ECL, et al. A prospective, randomized, pilot trial of a polyethylene glycol (PEG)-coated collagen patch (Hemopatch(®)) for intraoperative hemostasis during deceased donor renal transplant. Canadian Urological Association journal = Journal de l’Association des urologues du Canada. 2020;14(1):E1-e5.
7. Burghuber CK, Kandioler D, et al. Standardized intraoperative application of an absorbable polysaccharide hemostatic powder to reduce the incidence of lymphocele after kidney transplantation – a prospective trial. Transpl Int. 2019;32(1):59-65.
8. Dongol RM, Pahwa M, et al. Use of fibrin sealant in vein anastomosis in renal transplantation and its effect in preventing blood loss and postoperative peri-graft collection. International urology and nephrology. 2025;57(3):769-73.
9. Tammaro V, Vernillo A, et al. Prevention of fluid effusion in kidney transplantation with the use of hemostatic biomaterials. Transplant Proc. 2014;46(7):2203-6.