Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 9  |  Issue : 1  |  Page : 40-47

Chronic kidney disease and anticoagulation - Quick overview and practical guide


1 Vascular Surgery Unit, Department of Surgery, Christian Medical College and Hospital, Ludhiana, Punjab, India
2 Department of Vascular Surgery, Christian Medical College, Vellore, Tamil Nadu, India
3 Department of Vascular Surgery, Mayo Clinic, Rochester, Minnesota, USA
4 Department of Vascular Surgery, Sultan Qaboos University Hospital, Muscat, Oman
5 Department of Hematology, Sultan Qaboos University Hospital, Muscat, Oman
6 Department of Nephrology, Christian Medical College, Vellore, Tamil Nadu, India
7 Department of Nephrology, Sultan Qaboos University Hospital, Muscat, Oman

Date of Submission19-Aug-2021
Date of Acceptance28-Aug-2021
Date of Web Publication23-Mar-2022

Correspondence Address:
Edwin Stephen
Department of Vascular Surgery, Sultan Qaboos University Hospital, Muscat
Oman
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijves.ijves_90_21

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  Abstract 


Clinicians managing patients with chronic/end-stage renal disease often are challenged when it comes to anticoagulation in this subset. Unfractioned heparin and warfarin have been in use, and most multidisciplinary teams are comfortable with the drug/s either as prophylaxis or for full anticoagulation. Over the past decade, there has been an increase in the use of low-molecular-weight heparin and more recently of direct oral anticoagulants for anticoagulation. However, there is a reluctance to use these drugs for concern of increased bleeding and management of this complication in patients with renal disease. This paper shares a quick overview of coagulation in chronic/end-stage kidney disease and drugs used for anticoagulation, societal recommendations for their use, with clinical case scenarios, and a proposed management algorithm when patients have a bleed while on anticoagulation.

Keywords: Anticoagulation, chronic/end-stage renal disease, chronic kidney disease, direct oral anticoagulants, end-stage renal disease, low-molecular-weight heparin, unfractioned heparin


How to cite this article:
Pawar PP, Kota AA, Sen I, Stephen E, Al Rawahi B, Varughese S, Khan S. Chronic kidney disease and anticoagulation - Quick overview and practical guide. Indian J Vasc Endovasc Surg 2022;9:40-7

How to cite this URL:
Pawar PP, Kota AA, Sen I, Stephen E, Al Rawahi B, Varughese S, Khan S. Chronic kidney disease and anticoagulation - Quick overview and practical guide. Indian J Vasc Endovasc Surg [serial online] 2022 [cited 2022 May 28];9:40-7. Available from: https://www.indjvascsurg.org/text.asp?2022/9/1/40/340514




  Introduction Top


Chronic kidney disease (CKD) is a major global health problem affecting 8%–16% of adults globally. These patients are at increased risk for both arterial thromboembolism and venous thromboembolism (VTE). In addition, they are predisposed to arrhythmias, including atrial fibrillation (AF), atrial flutter, supraventricular tachycardias, ventricular tachycardias, and sudden cardiac death. Patients with CKD have an increased incidence of AF, with prevalence rates up to 21% in predialysis patients and 40% in dialysis patients.[1] These patients present a dilemma, in that they are simultaneously prothrombotic and have a tendency to bleed; therefore, a delicate balance is needed.

A few of the challenges are:

  • Need for anticoagulants is much higher in CKD
  • The advanced stages of CKD are frequently excluded from clinical trials, so there is no hard evidence on the safety and efficacy of anticoagulants
  • There are many disease-, patient-, and treatment-specific variables to be taken into consideration
  • There is no consensus among various societies, especially in advanced CKD stages 4 and 5.[2]


Vitamin K antagonists (VKAs) have been used for decades in patients with CKD who require anticoagulation. The current era has witnessed the wide scale use of direct oral anticoagulants (DOACs). In 2013, DOACs accounted for 62% of new prescriptions for anticoagulants in the USA. These drugs are as effective as VKAs, safer, simpler to use, and do not require routine monitoring. All the currently available DOACs depend, to varying extents, on renal function for clearance. Therefore, they can accumulate, leading to increased risk of bleeding. Their potential effectiveness and safety have also not been established as the pivotal trials have excluded advanced stages of CKD from their cohort.[3]

This paper briefly reviews the challenges of anticoagulant treatment in CKD, individual drug profiles in CKD, and societal recommendations for their use in CKD patients.


  Case Scenario 1 Top


A 43-year-old patient who had two failed renal transplants elsewhere presented to the hospital having had a third transplant, a month prior, with left leg swelling. His renal function was deranged, and he had a pseudoaneurysm at the transplant anastomosis site on the right external iliac artery (EIA). The previous transplant on the same side was from the internal iliac artery. He also had deep venous thrombosis (DVT) involving the distal external iliac, common femoral, and profunda femoris veins. Anticoagulation with unfractionated heparin (UFH) was started. A day later, he refused to allow samples to be taken for activated partial thromboplastin time (aPTT). As per hospital policy, enoxaparin is not prescribed for end-stage renal disease (ESRD) patients. This patient needed to have his transplanted kidney removed as it was not functioning and he was having a fever. The pseudoaneurysm was required to be treated before explanting the kidney, as did the proximal DVT [Figure 1]. Following covered stenting of the left EIA across the anastomotic site, the transplant kidney was explanted. No inferior vena cava filter was inserted.
Figure 1: Infarcted transplant kidney, pseudoaneurysm

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  Case Scenario 2 Top


A 66-year-old female was being dialyzed thrice weekly via a left brachiocephalic arteriovenous fistula. She was on rivaroxaban 15 mg alternate days for AF. She presented to the emergency department with a pulsatile swelling [Figure 2], with the overlying tense skin. Rivaroxaban was withheld for 24 h, and dialysis was performed via a temporary access. The rent in the cephalic vein required primary surgical repair and was used 2 weeks later. At discharge, she was started on warfarin.
Figure 2: Left brachiocephalic arteriovenous fistula pseudoaneurysm

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  Definition of Chronic Kidney Disease and Grading Top


According to the KDIGO guidelines, CKD is defined as abnormalities of the kidney structure or function, present for >3 months, with implications for health. CKD can be classified based on cause, glomerular filtration rate (GFR) category, and albuminuria category [Table 1].[4]
Table 1: Glomerular filtration rate categories in chronic kidney disease

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  Pathophysiology of Thromobosis and Bleeding in Chronic Kidney Disease Patients Top


Patients with CKD are at increased risk of AF, arterial thromboembolism and VTE, as well as bleeding, with risks increasing as renal function worsens. The age- and sex-standardized mortality rate ratio of pulmonary embolism (PE) has been reported to be 12 times higher in dialysis patients as compared to the general population.[5]

Factors associated with increased thrombosis are:

  • Uremic milieu promotes inflammation resulting in endothelial dysfunction, smooth cell proliferation, monocyte adhesion that favors calcification, and prothrombotic changes in the vascular endothelium
  • Increase in coagulation factors such as fibrinogen, von Willebrand factor, and factor VIII as part of the chronic inflammatory process
  • Increase in antifibrinolytic factors such as plasminogen activator inhibitor
  • Hyperlipidemia
  • Coagulation and platelet activation occurring in an extracorporeal hemodialysis device.[6]


The risk of bleeding is increased up to twofold if the estimated GFR falls below 30 ml/min. The annual risk for intracerebral hemorrhage in these patients is 6.2–10.2 per 1000 patients, which is well above the population frequency. The bleeding risk is due to platelet dysfunction, altered platelet-vessel wall interaction, anemia, heparin use in dialysis, and frequent use of antiplatelet medications in these patients.[5]


  Pharmacokinetics of Anticoagulant Drugs in Chronic Kidney Disease Top


Renal excretion is a major pathway for drug elimination by glomerular filtration and tubular secretion. CKD generally reduces both glomerular filtration and tubular secretion, which may lead to drug accumulation, requiring dose reduction or prolongation in the administration interval.[7]

The most commonly used renal function estimation equations are the Cockcroft–Gault (CG) formula, the modification of diet in renal disease study, and the equation from the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI). Although most of the clinicians prefer the CKD-EPI, all pivotal trials were done using the CG formula. There can be striking differences in the derived GFR values between the two formulas, leading to potential for drug dosing errors. Therefore, for DOAC dosing, the creatinine clearance (CrCl) should be calculated by the CG formula even though it overestimates the value by 10%–40%.[3] It is important to note that the CrCl estimations from these formulas are valid only when the patient's creatinine is in a steady state. Drug dosing in acute kidney injury should be individualized until the creatinine level stabilizes.[8]

Historically, warfarin has been the preferred anticoagulant in CKD, but with the increase in the use of DOACs, it is pertinent to assess the patient's renal function and to keep in mind the renal pharmacokinetics (PK) of the DOAC prescribed.


  Commonly Used Anticoagulant Drugs, Mechanism of Action, Monitoring, and Reversal Top


  1. VKAs


    • Warfarin
    • Nicoumalone


  2. Heparins


    • UFH
    • Low-molecular weight heparin (LMWH)
    • Synthetic Xa inhibitor
    • Fondaparinux


  3. Direct Xa inhibitor


    • Rivaroxaban
    • Apixaban
    • Edoxaban


  4. Direct thrombin inhibitor


    • Dabigatran.


Unfractionated heparin

UFH is a mixture of polyanionic branched glycosaminoglycans with a wide range of molecular weight (mw) between 6000 and 30,000 Da (mean mw 15,000). Administered in pharmacological doses, 30% of UFH binds to antithrombin (AT) with high affinity, thus leading to a conformational change, which converts AT from a slow to a very rapidly (1000 times) acting inhibitor of thrombin. Apart from thrombin, AT interacts with coagulation factors Xa and other components of plasmic hemostasis such as factors IXa, XIa, and XIIa, plasmin, kallikrein and trypsin.[9]

Clearance of UFH is primarily by the reticuloendothelial system in a rapid dose-dependent saturation mechanism and secondarily by a nonsaturable mechanism through the kidneys. The half-life of UFH is dose dependent ranging from 30 to 150 min and can be rapidly neutralized by protamine sulfate.

The main limitations of UFH are:

  • Unpredictable bioavailability
  • Frequent need to monitor aPTT to maintain therapeutic levels
  • Immune-mediated platelet activation leading to heparin-induced thrombocytopenia
  • Adverse effects of long-term treatment such as osteoporosis.[9]


Over anticoagulation can occur in patients with moderate (CrCl 30–50 ml/min) to severe (CrCl <30 ml/min) impairment in renal clearance once the reticuloendothelial saturation occurs. A conservative dosing of UFH is recommended in patients of severe renal impairment, with target aPTT to be maintained as per the condition that is being treated.[6]

Despite the extensive experience with UFH in daily practice, little evidence is available to confirm the safety of UFH in this high-risk group. An analysis of the large randomized controlled trials, ESSENCE and TIMI 11b, investigated the safety of enoxaparin and UFH treatment of acute coronary syndrome (ACS) in patients with a CrCl <30 ml/min. A total of 143 patients previously randomized to UFH or LMWH, enoxaparin 1 mg/kg, were retrospectively analyzed. The rates of major bleeding were 1.1% and 6.6% (P < 0.0001) in patients with CrCl >30 ml/min and <30 ml/min, respectively, with no difference in bleeding risks with UFH or unadjusted enoxaparin groups. The analysis demonstrates that the bleeding risk in patients with CKD (CrCl <30 ml/min) is greater than in patients with CrCl >30 ml/min, regardless of the anticoagulant used.[10]

The advantage of UFH in severe kidney disease is the ease of control of bleeding due to the lower half-life and complete reversal with protamine sulfate.[6],[10]

Low-molecular-weight heparins

LMWHs are synthesized through chemical or enzymatic depolymerization of UFH, resulting in shorter heparin chains that show stronger affinity for inhibiting factor Xa and lower specificity toward thrombin. The advantages of LMWH include predictable PK and anticoagulation response, the convenience of once- and twice-daily dosing regimens, lack of routine monitoring required, and a good track record of safety and efficacy in practice.[6]

LMWHs are among the preferred anticoagulants for preventing and treating venous thrombosis. A meta-analysis of randomized controlled trials showed similar efficacy between LMWH and UFH for acute DVT treatment and no bleeding risk difference but a reduced mortality rate in favor of LMWH.[11] LMWHs are replacing UFH as the first-line treatment for PE and unstable angina, a choice mainly due to their predictable effect and convenient use. LMWH is mainly cleared through the kidneys, leading to potential bioaccumulation and an increased risk of hemorrhage. Renal clearance is indirectly proportional to the mw of the drug. Therefore, a LMWH with a lower mw is more dependent on renal clearance and may accumulate in patients with renal dysfunction.[6],[12]

Enoxaparin

It is the most studied LMWH in patients with renal dysfunction, primarily due to its Food and Drug Administration (FDA)-licensed dose reduction (1 mg/kg once daily) for patients with severe renal disease (CrCl <30 ml/min). Care must be taken, however, to avoid subtherapeutic treatment in renal patients. Bleeding risks should be minimized but not at the risk of increasing further ACS or VTE events. Under-dosing, defined as peak anti-Xa levels <0.5 IU/ml, has been shown to occur in approximately one-fourth of patients on the dose-adjusted enoxaparin treatment (1 mg/kg once daily). Anti-Xa monitoring is therefore essential for enoxaparin. Current guidelines suggest target peak anti-Xa concentrations of 1.0–2.0 IU/ml if the medication is administered every 24 h and 0.5–1.0 IU/ml if dosing takes place every 12 h. Peak concentrations should be drawn 4–6 h after the third dose of enoxaparin.[6]

Enoxaparin dosing recommendations approved by the FDA have been shown to be associated with an increased incidence of bleeding in patients with renal impairment. A prospective randomized study by Barras et al. compared bleeding events in conventional (product-label) enoxaparin dosing to individualized dosing. The dosing scheme followed by the authors included the following fractions of the usual daily dose based on CrCl once a day:

  • 50 ml/min or greater: 1.0 mg/kg
  • 40–49 ml/min: 0.6 mg/kg
  • 30–39 ml/min: 0.5 mg/kg
  • 20–29 ml/min: 0.4 mg/kg
  • 10–19 ml/min: 0.3 mg/kg.


A total of 122 patients were studied, and patients in the individualized dosing group had fewer bleeding events. From the results of this study, we can infer that patient safety may be compromised without dose adjustment of enoxaparin starting at a CrCl of less than 50 mL/min.[13],[14]

Dalteparin

The data on bioaccumulation with LMWHs other than enoxaparin is limited. In a prospective cohort study of critically ill patients with a wide range of renal functions, including some with acute renal failure who required hemodialysis, dalteparin bioaccumulation was not observed despite repeated dosing. In a more recent study, subcutaneous dalteparin (5000 IU) was given daily to consecutive intensive care unit patients who had an estimated CrCl of 30 ml/min. There was no evidence of drug accumulation, nor was the risk of bleeding increased.[15],[16]

The evidence of its use in ACS/VTE in CKD patients is very limited, and further studies are required before its use can be recommended.[6]

In the setting of severe renal insufficiency where therapeutic anticoagulation is required, the use of UFH avoids the problems associated with impaired clearance of LMWH preparations. Although there is no specific CrCl threshold at which the risk for LMWH accumulation becomes clinically significant, an estimated CrCl of about 30 ml/min is a reasonable cutoff value based on the available literature.[17]

Tinzaparin

Tinzaparin has an mw of 6500 Da, which is the highest among all the LMWHs. Its elimination is less dependent on renal function as it is also metabolized through the reticuloendothelial system. Based on available PK data, there is consistent evidence that standard therapeutic doses of tinzaparin (175 IU/kg once daily) causes no clinically significant accumulation of anti-Xa activity in patients with a CrCl ≥20 ml/min. This suggests that there is no need for systematic anti-Xa activity monitoring or dosage adjustment of tinzaparin in these patients.[18]

In summary, if an LMWH is chosen for these patients, anti-Xa monitoring and/or dose reduction should be considered to ensure that there is no accumulation. In the case of enoxaparin, dose reduction may be used in patients with CrCl of 30 ml/min. The recommended treatment dose of enoxaparin for patients with a CrCl of 30 mL/min who have ACSs or VTE is 50% of the usual dose (i.e., 1 mg/kg once daily). No specific recommendations have been made for other LMWH preparations.

Warfarin

Warfarin has traditionally been the oral anticoagulant of choice due to clinician familiarity. There are some unique renal-specific factors which should be borne in mind with its use in CKD patients.

  • Lower dose requirements: Patients with severe renal dysfunction require a significantly lower daily dose of warfarin to achieve therapeutic international normalized ratio (INR) in comparison to control of normal kidney function. Patients with a CrCl of 30–59 ml/min/1.73 m2 tend to need a 10% lower maintenance dose, while those with levels of <30 ml/min/1.73 m2 require a 20% lower dose[6]
  • Labile INRs: CKD patients spent a longer time outside of the target INR and were at the highest risk of supratherapeutic anticoagulation (INR >4). This, in the setting of bleeding risk, put such patients at a higher risk of bleeding[6]
  • Risk of vascular calcification: Renal failure is associated with hyperphosphatemia, which can stimulate vascular smooth muscles in the arterial walls to develop osteoblastic characteristics, leading to calciphylaxis, a condition characterized by calcification, and thrombosis of the dermal arteries and painful skin lesions and ulcerations[6]
  • Warfarin-related nephropathy is thought to be due to glomerular hemorrhage and tubular obstruction caused by red cell casts. It is defined as an unexplained increase in serum creatinine >0.3 mg/dl within 7 days of INR >3.0 in a patient treated with warfarin.[6]


The use of warfarin in CKD has been mainly in patients with concomitant AF. Population-based studies suggest that AF occurs in around 1 in 5 patients with CKD and 1 in 3 in patients on dialysis. Before initiating warfarin anticoagulation, the use of scoring systems (CHA2DS2-VASc and HAS-BLED) to estimate thromboembolic and bleeding risk is mandatory. However, neither of these scoring systems accurately take into account loss of renal function and are unreliable when it comes to this cohort of patients.[19],[20],[21]

In mild-to-moderate CKD, the present evidence on anticoagulation suggests that it is safe and confers a benefit; however, in CKD stages 4 and 5, the net benefit has not been studied prospectively. Despite an FDA black box warning for warfarin use in patients with kidney dysfunction due to increased risk of major bleeding, it is still commonly used. Furthermore, clinical practice guidelines continue to recommend warfarin in treating AF among patients with CKD and patients with ESRD.

Direct oral anticoagulants

Historically, warfarin has been the preferred anticoagulant used in severe CKD, but with the concerns discussed above, more appropriate alternatives were sought. Co-existing renal impairment can often lead to uncertainty in choosing the best DOAC. Dabigatran is mostly eliminated by kidneys (80%), followed by edoxaban, rivaroxaban, apixaban, and betrixaban - 50%, 35%, 27%, and 11%, respectively. Any clinical decisions on how to treat patients with DOACs require the assessment of patient renal function, which should be monitored frequently, at least annually or more frequently as per guidelines.[22],[23]

Apixaban

Apixaban is a factor Xa inhibitor which is FDA approved for risk reduction of stroke/ systemic embolization in AF, treatment of VTE and prophylaxis of VTE post-hip and knee replacement. With serum creatinine ≥1.5 mg/dl and either age ≥80 years, or bodyweight ≤60 kg, a reduced dose of 2.5 mg twice daily is recommended.[22] The ARISTOTLE trial included 269 patients with CrCl 25–30 ml/min, which is the only set of randomized data comparing a DOAC with warfarin in a population with CrCl <30 ml/min. Patients with CrCl 25–30 ml/min randomized to apixaban, when compared with warfarin, experienced fewer major bleeding events and fewer major and clinically relevant nonmajor bleeding events. The drug label was amended in January 2014 to include approval for use in patients with renal impairment, including those on dialysis. These recommendations were based on single-dose PK studies, which revealed that CKD patients had 36%–44% more drug exposure than normal patients. In terms of dialysis clearance, only 6.7% of apixaban is cleared by a 4-h session, likely equally with use of high- or low-flux dialyzers. Additional work is needed to study the steady-state drug levels with long-term use in patients on hemodialysis.[24]

Rivaroxban

Rivaroxaban is a factor Xa inhibitor and is FDA approved in patients with AF to prevent stroke or systemic embolism, treatment of DVT and pulmonary embolism (PE) and prophylaxis after knee and hip replacement. It is prescribed at a fixed oral dose with 20 mg/day for patients with CrCl >50 ml/min and 15 mg/day for patients with CrCl 15–50 ml/min. It should be avoided in patients CrCl <15 ml/min. A subgroup analysis of the Rivaroxaban, Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation with impaired CrCl (<80 ml/min) reported no effect of kidney disease on rivaroxaban's effectiveness and safety. A PK study of a single 10-mg dose was conducted in 24 patients with CKD (CrCl <80 ml/min) and eight healthy controls (CrCl ≥80 ml/min). Compared with controls, the areas under the curve were 1.4-, 1.5-, and 1.6-fold higher with creatinine clearances of 50–80, 30–50, and <30 ml/min, respectively. This suggested that reduced rivaroxaban clearance with worsening creatinine clearance resulted in increased drug exposure. Rivaroxaban is likely to accumulate in patients with CKD and patients with end stage kidney disease even at lower doses (10 or 15 mg/day), and it is poorly cleared by hemodialysis.[22],[25],[26]

Dabigatran

Dabigatran is a direct thrombin inhibitor and was the first FDA-approved DOAC, at a dose of 150 mg twice per day for CrCl >30 ml/min. The drug has a renal clearance of at least 80% and is thus highly dependent on the kidney for removal from the body. In a subgroup analysis from the RE-LY study, in relation to renal function, cubic splines were used to model the rate of major bleeding by CrCl for warfarin and 150 mg of dabigatran. There was no statistical difference in bleeding between the two drugs. However, the rate of major hemorrhage among dabigatran-treated patients accelerated and surpassed warfarin when the CrCl fell below 50 ml/min. Thus, all dosing guidelines advise caution with dabigatran when CrCl is between 30 and 50 ml/min. Dabigatran is also the only dialyzable DOAC. A 4-h hemodialysis session will remove 50%–60% of plasma dabigatran, with a 10% rebound in dabigatran levels postdialysis.[3],[27]

Reversal of antithrombotic effect of direct oral anticoagulants [Algorithm 1]



Dabigatran being highly dialyzable allows hemodialysis as a treatment for dabigatran removal when the severity of bleeding necessitates faster drug clearance, and it is deemed unsafe to wait for the drug to be completely eliminated by the native kidneys.

In patients with life-threatening bleeding who need immediate dabigatran reversal, physicians may consider idarucizumab, a monoclonal antibody shown to neutralize the anticoagulant effect of dabigatran within 30 min. Idarucizumab is partially dependent on the kidney for elimination but is approved for patients with kidney disease.[28]

The anticoagulant effects of warfarin, apixaban, rivaroxaban, and edoxaban can be reversed by four-factor prothrombin complex concentrate, which can replace coagulation factors faster than fresh-frozen plasma (FFP), with less volume overload. Actively bleeding patients can be given desmopressin.[3]

Andexanet alfa, if available, can be used as a reversal agent for rivaroxaban and apixaban. This is a genetically modified factor Xa protein that binds and neutralizes Xa inhibitors. This is used only for life-threatening bleeding as an intravenous (IV) bolus and 2-h infusion, its use is limited by cost. The ANNEXA-4 study reported a 30-day thrombosis rate of 10%, although this was not specific to patients with renal failure.[29]

Although most anticoagulants have been used in patients with renal failure, majority of the guidelines have no definite recommendations for anticoagulation in those on dialysis and this remains an area of future research.[30] The NOAC dosing in CKD according to various societal guidelines is summarized in [Table 2].
Table 2: Various societal guidelines on use of anticoagulation in chronic kidney disease in atrial fibrillation

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Dosages of the reversal agents

Protamine sulfate for

Reversal of unfractionated heparin

  • Administered as a slow IV bolus dose at depending on time elapsed from last dose
  • Immediate: 1–1.5 mg/100 U of heparin, not to exceed 50 mg
  • 30–60 min: 0.5–0.75 mg/100 U heparin
  • >2 h: 0.25–0.375 mg/100 U heparin
  • Monitor aPTT 15 min after the dose and then again from 2 to 8 h
  • Complex of protamine and heparin may degrade over time requiring repeat doses.[31]


Reversal of low-molecular-weight heparin

  • Only partial (60%) reversal of anti-factor Xa activity
  • 1 mg for 100 U of dalteparin or tinzaparin
  • 1 mg per mg of enoxaprin if <8 h; if >8 h, then 0.5 mg per mg of enoxaparin.[31]


Vitamin K1

  • If serious or life-threatening bleeding at any INR withhold VKA's and give 10 mg Vitamin K1 intravenously slowly over 10 min augmented by FFP's and 4- factor prothrombin complex concentrate. Vitamin K can be repeated every 12 h
  • Oral Vitamin K can be given if INR is deranged to a lesser degree.[31]


Idarucizumab

  • Intravenous (IV) administration of two separate 2.5 g vials no more than 15 min apart for emergency surgeries or life-threatening/uncontrollable bleeding in patients on dabigatran.[32]


Andexanet alfa

  • If the last dose of rivaroxaban and apixaban is <10 mg or 5 mg, respectively, and the time since last dose is >8 h, then administer the low-dose regimen. The regimen is 400 mg IV bolus at 30 mg/min followed by a 2 h infusion at 4 mg/min
  • If the last of rivaroxaban and apixaban is >10 mg or 5 mg, respectively, and the time since last dose is <8 h, then administer the high-dose regimen. The regimen is 800 mg IV bolus at 30 mg/min followed by a 2-h infusion at 8 mg/min.[33]



  Conclusion Top


There are more questions than answers in the management of anticoagulation in CKD patients, and this presents a unique challenge to the treating physician. With the increase in the use of DOACs across various specialties, coupled with the increasing incidence of CKD, it is imperative to be up to date and informed about the PK and pharmacodynamics of the various anticoagulant agents. Dynamic and individualized treatment of these patients with close consultation of the nephrologist remains the recommended approach. Lack of uniform and fixed recommendations in existing venous thrombosis guidelines suggests a dearth of information, but this presents itself as a unique research and learning opportunity.[35]

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the legal guardian has given his consent for images and other clinical information to be reported in the journal. The guardian understands that names and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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