Anticoagulation in hemodialysis

Anticoagulation in hemodialysis
Dr.

Scope Introduction Anticoagulation for hemodialysis Newer developments
Coagulation cascade Hemostatic abnormalities in renal insufficiency Anticoagulation for hemodialysis Unfractionated heparin No heparin dialysis LMWH Regional anticoagulation Newer developments Conclusions

Introduction Adequate anticoagulation in hemodialysis procedures relies on Knowledge of the Basic principles of hemostasis and notably the clotting cascade Hemostatic abnormalities in renal insufficiency as well as activation of clotting on artificial surfaces Hemodialysis International 2007; 11:178–189

Introduction Hemostasis defined as a
Process of fibrin clot formation to seal a site of vascular injury without resulting in total occlusion of the vessel Multiple processes including both cellular elements and numerous plasma factors with enzymatic activity is arranged (1) to activate clotting rapidly, (2) to limit and subsequently terminate this activation, and (3) to remove the clot by fibrinolysis in the end Hemodialysis International 2007; 11:178–189

Introduction The initial hemostatic response to stop bleeding is the
Formation of a platelet plug at the site of vessel wall injury Platelets are activated by Multitude of stimuli, the most potent of which are Thrombin and collagen Upon activation, platelets Adhere to the subendothelial matrix, aggregate, secrete their granule content, and expose procoagulant phospholipids such as phosphatidylserine Hemodialysis International 2007; 11:178–189

Introduction Platelet-derived membrane microvesicles
Markedly increase the phospholipid surface on which coagulation factors form multimolecular enzyme complexes with procoagulant activity Hence, platelet activation also Leads to propagation of plasmatic coagulation Hemodialysis International 2007; 11:178–189

Coagulation Cascade Coagulation Cascade
Complex, multiply redundant and includes intricate checks and balances Hemodialysis International 2007; 11:178–189

Coagulation Cascade Intrinsic pathway Extrinsic pathway
Activated by damaged or negatively charged surfaces and the accumulation of kininogen and kallikrein The activated partial thromboplastin time (APTT) tends to reflect changes in the intrinsic pathway Extrinsic pathway Triggered by trauma or injury, which releases tissue factor The extrinsic pathway is measured by the prothrombin test Hemodialysis International 2007; 11:178–189

Hemostatic abnormalities in renal insufficiency
The accumulation of uremic toxins causes complex disturbances of the coagulation system Uremia can lead to an increased bleeding tendency, e.g., Due to platelet dysfunction which is further enhanced with use of anticoagulants during extracorporeal blood purification procedures Hemodialysis International 2007; 11:178–189

Clot formation and development of thrombosis can also occur at increased rates in dialysis patients Pulmonary embolism is more frequent in dialysis patients than in age-matched controls Hemodialysis International 2007; 11:178–189

Patients on chronic intermittent hemodialysis frequently suffer from Vascular access thrombosis, the risk of which is increased in Polytetrafluoroethylene grafts compared with arteriovenous fistulas

Anticoagulation for hemodialysis (HD)
Anticoagulation is routinely required to prevent clotting of The dialysis lines and dialyser membranes, In both acute intermittent haemodialysis and continuous renal replacement therapies Field of anticoagulation is constantly evolving Important to regularly review advances in knowledge and changing practices in this area Semin. Dial. 2009; 22: 141–5

Anticoagulation for HD
The responsibility for prescribing and delivering anticoagulant for HD is shared between the Dialysis doctors and nurses Dialysis is a medical therapy Must be prescribed by an appropriately trained doctor Nephrology 2010;15:386–392

The prescribing doctor usually determines which anticoagulant agent will be used and the dosage range The doctor’s prescription may include broad instructions such as ‘no heparin’, ‘low heparin’ or ‘normal heparin’ Nephrology 2010;15:386–392

In a mature dialysis unit the dose and delivery of anticoagulant is, however, the responsibility of professional and experienced dialysis nurses, who have latitude within parameters determined by detailed written policies or standing orders Nephrology 2010;15:386–392

Dosing regimens, while generally safe and effective, are somewhat unscientific In terms of monitoring Most units do not practise routine monitoring, Although the anticoagulant effect of unfractionated heparin (UF heparin) can be monitored with some accuracy by the APTT or the activated clotting time tests where indicated Nephrology 2010;15:386–392

The dialysis nurses Know - too much anticoagulation if The needle sites continue to ooze excessively for a prolonged period (e.g. more than 15 min) after dialysis Know - too little anticoagulation if ‘streaking’ in the dialyser, excessively raised transmembrane pressure or evidence of thrombus in the venous bubble trap – indicated by dark blood, swelling of the trap or rising venous pressure Nephrology 2010;15:386–392

The nurses Know that patients dialysing with a venous dialysis catheter are at greater risk of thrombosis With some trial and error, The right dose of anticoagulant for any patient can be empirically determined Nephrology 2010;15:386–392

In normal circumstances effective and safe anticoagulation for HD can be delivered with Low risk and high efficiency Nephrology 2010;15:386–392

Unfractionated heparin
Constitute a mixture of anionic glucosaminoglycans of varying molecular size (5–40, mean 15 kDa) Mechanism: Indirect due to the binding to antithrombin (‘‘heparin-binding factor I’’) Heparin enhances the activity of this natural anticoagulant protein 1000 to 4000-fold Antithrombin inactivates thrombin, factor Xa, and to a lesser extent factors IXa, XIa, and XIIa At high doses, heparin also binds to ‘‘heparin-binding factor II” Nephrology 2010;15:386–392

Heparin can be directly procoagulant through platelet activation and aggregation However, its main effect is anticoagulant, through its binding to anti-thrombin (antithrombin III or heparin-binding factor I) At high doses heparin can also bind to heparin-binding factor II – which can directly inhibit thrombin When heparin binds antithrombin it causes a conformation change, which results in a 1000–40 000¥ increase in the natural anticoagulant effect of anti-thrombin Nephrology 2010;15:386–392

Heparin is ineffective against thrombin or factor Xa If they are located in a thrombus or bound to fibrin or to activated platelets UFH has a narrow therapeutic window of adequate anticoagulation without bleeding, Laboratory testing (aPTT or as bedside test ‘‘activated clotting time,’’ ACT) of its effect is required Nephrology 2010;15:386–392

First isolated from liver (hepar) mast cells of dogs Now commercially derived from porcine intestinal mucosa or bovine lung When administered intravenously Half-life approx. 1.5 h Highly negatively charged and binds non-specifically to endothelium, platelets, circulating proteins, macrophages and plastic surfaces Nephrology 2010;15:386–392

In addition to removal by adherence, heparin is cleared by both renal and hepatic mechanisms and is metabolized by endothelium

Interestingly, UF heparin has both pro- and anti-coagulant effects At high doses heparin can also bind to heparin-binding factor II – which can directly inhibit thrombin When heparin binds antithrombin it causes a conformation change, which results in a 1000–40 000x increase in the natural anticoagulant effect of anti-thrombin.

Heparin-bound anti-thrombin inactivates multiple coagulation factors including covalent binding of thrombin and Xa and lesser inhibition of VII, IXa, XIa, XIIa. By inactivating thrombin, UF heparin inhibits thrombininduced platelet activation as well Of note, UF heparinbound anti-thrombin inactivates thrombin (IIA) and Xa equally Only UF heparin with more than 18 repeating saccharide units inhibits both thrombin and Xa, whereas shorter chains only inhibit Xa.

For haemodialysis, UF heparin can be administered, usually into the arterial limb, according to various regimens, but Most commonly is administered as a loading dose bolus followed by either an infusion or repeat bolus at 2–3 h The initial bolus is important to overcome the high level of non-specific binding, following which there is a more linear dose : response relationship

The loading dose bolus may be 500 units or 1000 units and infusion may vary from 500 units hourly to 1000 units hourly, depending on whether the prescription is ‘low dose heparin’ or ‘normal heparin’ Heparin administration usually ceases at least 1 h before the end of dialysis

The most important risk of UF heparin is the HIT syndrome (HIT Type II) Other risks or effects attributed to UF heparin that have been reported include hair loss, skin necrosis, osteoporosis, tendency for hyperkalaemia, changes to lipids, a degree of immunosuppression, vascular smooth muscle cell proliferation and intimal hyperplasia Beef-derived heparin can be a risk for the transmission of the prion causing Jacob Creutzfeld type encephalopathy

Use of UF heparin is Safe, simple and inexpensive and Usually encounters few problems However, there are risks with HD anticoagulation which are important to be aware of and include The risk of bleeding Some risks are not immediately obvious – such as inadvertent over-anticoagulation in high-risk patients because of excessive heparin volume used to lock the venous dialysis catheter at the end of dialysis Nephrology 2010;15:386–392

The disadvantages of UF heparin may include Lack of routine or accurate monitoring of anticoagulation effect The need for an infusion pump and the costs of nursing time Perhaps the most important risk is that of Heparin-induced thrombocytopaenia (HIT Type II), which is greatest with the use of UF heparin Nephrology 2010;15:386–392

At times the routine anticoagulation prescription needs to be varied Additional choices include ‘no heparin’ dialysis, the use of low-molecular-weight heparin (LMWH) instead of UF heparin, and the use of regional anticoagulation New agents and new clinical variations appear in the literature continuously Nephrology 2010;15:386–392

No Heparin Dialysis Dialysis without anticoagulation may be indicated in patients with High risk of bleeding Acute bleeding disorder Recent head injury Planned major surgery Trauma Acute HIT syndrome or Systemic anticoagulation for other reasons Nephrology 2010;15:386–392

No Heparin Dialysis The procedure involves
Multiple flushes of 25–50 ml of saline every 15–30 min, in association with a high blood flow rate In some units the lines are pretreated with 2000–5000 U of UF heparin and then flushed with 1 L of normal saline, to coat the lines This form of dialysis anticoagulation is Very labour-intensive and Usually only partially effective Nephrology 2010;15:386–392

No Heparin Dialysis No Heparin Dialysis
Partial clotting still occurs in 20% of cases with complete clotting of lines or dialyser, requiring Line change in 7% of ‘no heparin’ dialyses The risk of clotting may be exacerbated by Poor access blood flow, the use of a venous catheter, hypotension or concomitant blood transfusion Where a venous catheter is used, there is an increased risk of catheter occlusion ‘No heparin’ dialysis may also provide less effective dialysis and result in lower clearances Nephrology 2010;15:386–392

Low molecular weight heparin (LMWH)
Depolymerized fractions of heparin can be obtained by Chemical or enzymatic treatment of UF heparin Anionic glycosaminoglycans but have a lower molecular weight of 2–9 kDa, 5 kDa – thus consisting of ≤ 15 saccharide units The shorter chain length results in Less coagulation inhibition, but Superior pharmacokinetics, higher bioavailability, less non-specific binding and longer half-life, all of which help to make LMWH dosage simpler and more predictable than UF heparin Nephrology 2010;15:386–392

LMWH LMWH In addition Less impact on platelet function, and thus may cause less bleeding Binds anti-thrombin III and inhibits factor Xa, But most LMWH (50–70%) does not have the second binding sequence needed to inhibit thrombin because of the shorter chain length Nephrology 2010;15:386–392

LMWH In most cases the affinity of LMWH for Xa versus thrombin is of the order of 3:1 The anticoagulant effect of LMWH can be monitored by the anti-factor Xa activity in plasma Nephrology 2010;15:386–392

LMWH LMWH Cleared by renal/dialysis mechanisms, so dosage must be adjusted to account for this When high flux dialysers are used, LMWH is more effectively cleared than UF heparin Often administered into the venous limb of the dialysis circuit Nephrology 2010;15:386–392

Enoxaparin One of the most commonly used LMWH
Has the longest half-life Predominantly renally cleared Dose reduction need to be made in the elderly, in the presence of renal impairment and in very obese patients, to avoid life-threatening bleeding Nephrology 2010;15:386–392

Enoxaparin Generally does not accumulate in 3/week dialysis regimens, but there is a risk of accumulation in more frequent schedules No simple antidote and in the case of severe haemorrhage- Activated factor VII concentrate may be required Nephrology 2010;15:386–392

Enoxaparin On the other hand patients dialysing with a high flux membrane, as compared with a low flux membrane, May require a higher dose because of dialysis clearance Effect and accumulation can be monitored by the performance of anti-Xa levels Nephrology 2010;15:386–392

Enoxaparin A common target range is More conservative range
0.4– 0.6 IU/ml anti-Xa but a More conservative range 0.2– 0.4 IU/ml is recommended in patients with a high risk of bleeding The product insert should always be consulted Nephrology 2010;15:386–392

Enoxaparin The use of LMWH such as enoxaparin for HD anticoagulation is Well supported in the literature Enoxaparin can be administered as a Single dose and generally does not require to be monitored Yet unclear whether enoxaparin can successfully anticoagulate patients for long overnight (nocturnal) HD Against the utility of LMWH, the purchase price of LMWH still significantly exceeds UF heparin Nephrology 2010;15:386–392

LMWH The other available forms of LMWH e.g.
Dalteparin, Nadroparin, Reviparin Tinzaparin and newer LMWH vary somewhat, especially in Anti-Xa/anti-IIa effect The higher this ratio the more Xa selective the agent and consequently the less effect protamine has on reversal Enoxaparin High anti-Xa/anti-IIa ratio of 3.8, and is < 60% reversible with protamine Nephrology 2010;15:386–392

Is LMWH better? Significance is
Lower incidence of HIT Type II, a devastating and deadly complication, in patients exposed to LMWH compared with UF heparin Another advantage of LMWH is the Longer duration of action and predictability of dosage effect, allowing the convenience of a single subcutaneous injection at the start of dialysis without the need for routine monitoring Nephrology 2010;15:386–392

Is LMWH better? The use of LMWH is reported to cause
Less dialysis membrane-associated clotting, fibrin deposition and cellular debris LMWH has less non-specific binding to platelets, circulating plasma proteins and endothelium Nephrology 2010;15:386–392

Is LMWH better? UF heparin induces
Inhibition of mineralocorticoid metabolim and reduced adrenal aldosterone secretion, but LMWH has been shown to have less inhibition in this regard Other deleterious effects associated with UF heparin are also generally less common with the use of LMWH including The risk of osteoporosis, hair loss, endothelial cell activation and adhesion molecule activation Nephrology 2010;15:386–392

Is LMWH better? A meta-analysis including 11 studies was published in 2004 and showed that LMWH and UF heparin were similarly safe and effective in preventing extracorporeal circuit thrombosis, with No significant difference in terms of bleeding, vascular compression time or thrombosis J. Am. Soc. Nephrol. 2004; 15: 3192–206.

Is LMWH better? LMWH is however recommended as the agent of choice for routine haemodialysis by the European Best Practice Guidelines The single factor weighing against the use of LMWH as the routine form of anticoagulation for dialysis is cost More and more dialysis units are assessing the cost/benefit ratio as in favour of the routine use of LMWH for haemodialysis Because of the potency, ease of administration, predictable clinical effect and low rate of side effects Nephrology 2010;15:386–392

Anti-Xa monitoring May be used for dosing adjustment of LMWH, to ensure therapeutic dosing or to exclude accumulation prior to a subsequent dialysis Because of the high bioavailability, dose-independent clearance by renal mechanisms, and predictable effect, there is generally no need to monitor routinely. Nephrology 2010;15:386–392

Regional anticoagulation for HD
Aim of regional anticoagulation is To restrict the anticoagulant effect to the dialysis circuit and prevent systemic anticoagulation, For instance in patients at increased risk of bleeding Nephrology 2010;15:386–392

UF heparin/protamine Historically, the use of UF heparin/protamine was prototypical of regional anticoagulation UF heparin is infused into the arterial line and protamine into the venous line Protamine Basic protein that binds heparin, forming a stable compound and eliminating its anticoagulant effect Nephrology 2010;15:386–392

UF heparin/protamine Full neutralization of heparin can be achieved with A dose of 1 mg protamine/100 units heparin Protamine has a shorter half-life than heparin so There may be an increased risk of bleeding 2–4 h after dialysis Nephrology 2010;15:386–392

UF heparin/protamine Most authors agree that
Procedure can be technically challenging and No significant advantage over ‘low-dose’ heparin regimens Reactions to protamine are not uncommon and may be serious As all forms of heparin are absolutely contraindicated in HIT Type II this form of regional anticoagulation cannot be used in that syndrome Nephrology 2010;15:386–392

Citrate regional anticoagulation
Citrate binds ionized calcium and is a Potent inhibitor of coagulation Regional citrate regimens generally Utilize isoosmotic trisodium citrate or hypertonic trisodium citrate infusion into the arterial side of the dialysis circuit Nephrology 2010;15:386–392

This methodology Avoids the use of heparin and Limits anticoagulation to the dialysis circuit – Effects which can be used for routine dialysis in patients at increased risk of bleeding or for dialysis anticoagulation in the stable phase of HIT Type II Nephrology 2010;15:386–392

The citrate–calcium complex Partially removed by the dialyser The procedure may require, or be enhanced by, Use of calcium and magnesium-free dialysate A low bicarbonate dialysate is also recommended to Rreduce the risk of alkalosis, Especially in the setting of daily dialysis, as citrate is metabolized to bicarbonate Nephrology 2010;15:386–392

To neutralize the effect of citrate, Calcium chloride solution is infused into the venous return at a rate designed to correct ionized calcium levels to physiologic levels Plasma calcium must be measured frequently, e.g. second hourly, with prompt result turnaround Nephrology 2010;15:386–392

The procedure Complex and high risk Requirement for two infusion pumps and Point of care calcium measurement Either high or low calcium levels in the patient may risk severe acute complications Hypertonic citrate may risk hypernatraemia Metabolism of citrate generates a metabolic alkalosis Nephrology 2010;15:386–392

Nevertheless, the technique has been used with Great success in some hands, with Few bleeding complications and improved biocompatibility with reduced granulocyte activation and Less deposition of blood components in the lines or on the dialyser Simplified protocols have been proposed Nephrology 2010;15:386–392

Prostacyclin regional anticoagulation
Utilizes prostacyclin as a Vasodilator and platelet aggregation inhibitor Very short half-life of 3–5 min Infused into the arterial line Of importance Prostacyclin is adsorbed onto polyacrylonitrile membranes Side effects can include Headache, light headedness, facial flushing, hypotension and excessive cost Nephrology 2010;15:386–392

Heparin-induced thrombocytopaenia (HIT)
There are two well-described syndromes of HIT, the First relatively benign Second potentially devastating Nephrology 2010;15:386–392

HIT Type I HIT type I 10–20% of patients treated with UF heparin
Mild thrombocytopaenia occurs (< ) as a result of heparin activation of platelet factor 4 (PF4) surface receptors, leading to platelet degranulation Mechanism is non-immune and early in onset, after the initiation of heparin The syndrome generally resolves spontaneously within 4 days despite the continuation of heparin Generally no sequelae of clinical significance Nephrology 2010;15:386–392

HIT Type II HIT Type II Much more serious and devastating than HIT Type I Generally occurs within the first 4–10 days of exposure to heparin Late onset is less common Mechanism of HIT which results in both platelet activation and activation of the coagulation cascade Nephrology 2010;15:386–392

HIT Type II Severe platelet reduction occurs rapidly,
Generally platelet count remains > Clinical HIT Type II is reported to occur in 2–15% of patients exposed to heparin More commonly in females and surgical cases In dialysis patients the incidence varies between 2.8% and 12% Nephrology 2010;15:386–392

HIT Type II HIT Type II Occurs in incident patients or after re-exposure to heparin after an interval Of importance the incidence is 5–10 times more common with UF heparin than with patients receiving only LMWH The risk with LMWH is reportedly very low, in the order of <1% Nephrology 2010;15:386–392

HIT Type II HIT Type II Two clinical phases Acute phase Second phase,
Significant thrombocytopaenia and high risk of thromboembolic phenomena Avoidance of heparin and systemic anticoagulation are essential Second phase, Signalled by recovery of platelet levels, heparin must still be avoided (for a prolonged period if not forever) but systemic anticoagulation is not required Dialysis anticoagulation remains a challenge as all forms of heparin must be avoided Nephrology 2010;15:386–392

HIT Type II With the onset of HIT Type II, heparin must be immediately discontinued, even before confirmatory results are available Available tests for HIT Type II include detection of antibodies against heparin–PF4 complex, detection of heparin-induced platelet aggregation or platelet release assays – but none is totally reliable HIT acute phase will not resolve while heparin is continued and HIT will recur on rechallenge with either UF heparin or LMWH Once HIT is established after exposure to UF heparin, there is a >90% cross-reactivity with LMWH Nephrology 2010;15:386–392

HIT Type II Untreated, there is a major risk of venous and arterial thrombosis, estimated at >50% within 30 days Most of the clots are described as venous Arterial thrombi are often platelet-rich white thrombi (white clot syndrome) which can cause limb ischaemia and cerebral or myocardial infarcts Nephrology 2010;15:386–392

HIT Type II In patients with HIT Type II all heparin products must be avoided, including Topical preparations, coated products as well as intravenous preparations Systemic anticoagulation without heparin is mandatory in the acute phase For haemodialysis, patients may have ‘no heparin’ dialysis or anticoagulation with non-heparins The available agents commonly used include Danaparoid, Hirudin, Argatroban, Melagatran and Fondaparinux Nephrology 2010;15:386–392

HIT Type II Alternatively, regional citrate dialysis has proved effective in this setting Each approach or alternative agent provides its own challenges and there may be a steep learning curve. Both UF heparin and LMWH are contraindicated Venous catheters must not be heparin locked, but can be locked with recombinant tissue plasminogen activator or citrate ( trisodium citrate 46.7%) Other alternatives to consider may include switching the patient to peritoneal dialysis or using warfarin In the longer term it may be possible to cautiously reintroduce UF heparin, or preferably LMWH, without reactivating HIT Type II Nephrology 2010;15:386–392

Danaparoid Currently, this agent remains drug of choice in most Australian hospitals for HIT Type II, May have unique features, which interfere with the pathogenesis of HIT Type II Extracted from pig gut mucosa Heparinoid of molecular weight of 5.5 kDa 83% heparan sulphate, 12% dermatan sulphate and 4% chondroitin sulphate Nephrology 2010;15:386–392

Danaparoid Danaparoid More selective for Xa than even the LMWH
Binds to antithrombin (heparin cofactor I) and heparin cofactor II and has some endothelial mechanisms, but Minimal impact on platelets and a low affinity for PF4 More selective for Xa than even the LMWH (Xa : thrombin binding : Danaparoid 22–28 : 1; LMWH 3:1 typically) Low cross-reactivity with HIT antibodies (6.5–10%) although Recommended to test for cross-reactivity before use of Danaparoid in acute HIT Type II Nephrology 2010;15:386–392

Danaparoid Danaparoid No reversal agent
Very long half-life of about 25 h in normals Longer with chronic renal impairment (e.g. 30 h) No reversal agent Clinically, significant accumulation should be tested by Anti-Xa estimation before any invasive procedure Nephrology 2010;15:386–392

Hirudin Originally discovered in the saliva of leeches
Binds thrombin irreversibly at its active site and the fibrin-binding site Recombinant or synthetic variants are also available – including Lepirudin, Desirudin and Bivalirudin Hirudin and its cogeners are Polypeptides of molecular weight of 7 kDa with no cross-reactivity to the HIT antibody Nephrology 2010;15:386–392

Hirudin Hirudin Studies have confirmed Prolonged half-life
Renally cleared, so its half-life in renal impairment is > 35 h Studies have confirmed Hirudin can be used as an anticoagulant for HD Nephrology 2010;15:386–392

Hirudin Hirudin No cross-reactivity with UF heparin or LMWH; however,
Hirudin and its analogues are antigenic in their own right, and up 74% of patients receiving Hirudin i.v. can develop anti-Hirudin antibodies, which can further prolong the half-life Nephrology 2010;15:386–392

Hirudin Hirudin The APTT No antidote to Hirudin, but
Because of the tendency to form antibodies, difficult to use, as anaphylaxis can occur with a second course The APTT May be used to monitor Hirudin anticoagulant effect but The relationship is not necessarily linear No antidote to Hirudin, but Removed to some extent by haemofiltration/ plasmapheresis but not HD Nephrology 2010;15:386–392

Argatroban Synthetic derivative of L-arginine
Appears to be the treatment of choice in the USA Acts as a direct thrombin inhibitor and Binds irreversibly to the catalytic site Short half-life of 40–60 min Not effected by renal function Hepatic clearance means prolonged duration of action in patients with liver failure Nephrology 2010;15:386–392

Argatroban Anticoagulant effect can be monitored by a variant of the APTT – the ecarin clotting time No available reversal agent Nephrology 2010;15:386–392

Melagatran Direct thrombin inhibitor
Available orally as a prodrug, which is taken twice a day Renally cleared and has a prolonged half-life No antidote Nephrology 2010;15:386–392

Melagatran Reports of hepatotoxicity have impeded further drug development It has been suggested that Melagatran may have a role in anticoagulation between dialysis treatments in patients with HIT Type II Nephrology 2010;15:386–392

Fondaparinux Synthetic pentasaccharide of 1.7 kDa,
Copy of an enzymatic split product of heparin Synthetic analogue of the pentasaccharide sequence in heparin that mediates the anti-thrombin interaction High affinity for anti-thrombin III but No affinity for thrombin or PF4 Nephrology 2010;15:386–392

Fondaparinux Fondaparinux Can be administered i.v. or s.c.
Monitored by the use of anti-Xa testing With a prolonged half-life it can be administered alternate days Renally cleared, it may accumulate in renal failure Removed to some degree by high flux haemodialysis or haemodiafiltration Nephrology 2010;15:386–392

Conclusions Anticoagulation is an essential part of the safe and effective delivery of HD Physicians accredited to prescribe dialysis must have a fundamental understanding of anticoagulation therapy in different dialysis settings

Conclusions Essential for nephrologists to have a good understanding of The relative merits of UF heparin and LMWH, To develop an approach to the clinical management of HIT Type II and other important heparin-related complications

Conclusions Continuous development of new anticoagulant drugs and associated clinical recommendations This is an area that dialysis clinicians should revisit at timely intervals

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Anticoagulation in hemodialysis

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