Hirudin in heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia (HIT), a serious side effect of heparin treatment, requires alternative anticoagulation in most affected patients. The recombinant hirudin (r-hirudin) lepirudin has been approved for this purpose after two prospective trials in laboratory-confirmed HIT patients. Other drugs available for this purpose are danaparoid sodium (a heparinoid) and argatroban, a synthetic direct thrombin inhibitor. In this article, recommendations for optimal use of r-hirudin in HIT are given, covering therapy in uncomplicated patients as well as in special situations such as heparin reexposure of HIT patients. Because lepirudin's half-life depends on renal function, it may vary between 1 and 200 hours, which requires individual dose adjustments. Lepirudin compares favorably with danaparoid, based on retrospective data. No direct comparisons of lepirudin with argatroban are available, but argatroban might offer advantages in patients with renal failure, because it is mainly eliminated hepatically. Major hemorrhage, the main risk of lepirudin treatment, occurring in about 15% of patients, makes close monitoring important. New monitoring tools, such as the ecarin clotting time (ECT), might further reduce bleeding risks. Antihirudin antibodies, which can alter the pharmacokinetics as well as the pharmacodynamics of hirudin, can also be countered by close monitoring and appropriate dose adjustments. Whereas hirudins have not yet managed to gain importance in non-HIT indications such as unstable coronary syndromes, they have a major role to play in the treatment of HIT. The choice between the available drugs for HIT, namely lepirudin, danaparoid, and argatroban, has to be made according to the clinical presentation of the patient.     

Antikoagulation bei Nierenersatztherapie auf der Intensivstation

The choice of the form of anticoagulation in continuous renal replacement therapy (CRRT) in critically ill patients often depends on local factors and the individual clinical situation. Heparin is the form of anticoagulation most often used for CRRT for preventing thrombosis in the blood circulation. Critically ill patients have an increased likelihood of bleeding, making sufficient anticoagulation difficult. In cases of suspected or proven heparin-induced thrombopenia (HIT), therapeutic anticoagulation is recommended with direct thrombin inhibitors or danaparoid. Anticoagulation of CRRT can also be conducted with these agents but monitoring in critically ill patients is difficult, giving rise to bleeding complications and short circulation life. In contrast, regional anticoagulation with citrate does not have these disadvantages. Even in cases of HIT or after surgery CRRT can be continued without risk. Modern dialysis devices, adapted dialysates and simple monitoring help to prevent complications such as hypocalcemia or metabolic alkalosis. Therefore, regional anticoagulation with citrate will probably become the standard form of anticoagulation for CRRT in intensive care units.     

Lepirudin as a safe alternative for effective anticoagulation in patients with known heparin-induced thrombocytopenia undergoing percutaneous coronary intervention: case reports.

Heparin-induced thrombocytopenia (HIT) is a well-documented complication of heparin anticoagulation therapy. Heparin's frequent use in the cardiovascular population poses a significant challenge for managing patients with HIT in need of percutaneous coronary intervention (PCI). We describe four patients with HIT who successfully underwent PCI without thrombotic or hemorrhagic complications while on lepirudin.     

A comparison of lepirudin and argatroban outcomes.

Although both argatroban and lepirudin are used for the management of heparin-induced thrombocytopenia (HIT), data comparing these agents are lacking. The objective of this project was to compare the clinical outcomes of lepirudin vs argatroban therapy. Patients who received a direct thrombin inhibitor (DTI) from January 2000 to December 2001 were identified. Medical charts were retrospectively reviewed and relevant data extracted. The primary efficacy outcome was effective anticoagulation and the primary safety outcome was major bleeding. Data were analyzed using the t test and Fisher's exact test. Sixty-one lepirudin patients and 29 argatroban patients received a DTI during the study period. A new diagnosis of HIT was the indication for DTI therapy in 44.8% of argatroban patients and 57.4% of lepirudin patients. Effective anticoagulation was achieved in 77.8% of argatroban patients and 69.5% of lepirudin patients (p = .61). Major bleeding occurred in 10.3% and 11.5% of argatroban and lepirudin patients, respectively (p = 1.0). Argatroban and lepirudin demonstrated comparable safety and efficacy outcomes.     

Treatment of Patients with a History of Heparin-Induced Thrombocytopenia and Anti-Lepirudin Antibodies with Argatroban

Patients with heparin-induced thrombocytopenia (HIT) type II require anticoagulation with non-heparin immediate acting anticoagulants. Danaparoid may cross react with HIT-antibodies and lepirudin may generate anti-lepirudin antibodies influencing anticoagulation. We hypothesised, that the synthetic small molecular thrombin inhibitor argatroban does not induce immunoglobulins reacting towards lepirudin in patients with anti-lepirudin antibodies in the history and that titration of the anticoagulation may be easier with argatroban. We report on the treatment of four patients of a study, which was terminated prematurely due to official warnings for a repeated use of lepirudin. Two patients each received argatroban and lepirudin intravenously. A blinded assessor adjusted the doses of the anticoagulants to 1.5–3.0 fold prolongation of the aPTT. Ecarin clotting time (ECT), concentrations of lepirudin (ELISA) and of argatroban (gaschromatoraphy with mass spectrometry,) and the generation of lepirudin antibodies (ELISA) were measured. APTT-adjusted dosages for argatroban was 2.0–2.6 μg/kg⋅ min and for lepirudin 48–149 μ g/kg⋅ h. ECT was prolonged 2.1 to 4.5-fold with lepirudin and 4 to 7-fold with argatroban. The concentration of lepirudin ranged between 750 and 1500 ng/ml and of argatroban between 400 and 1100 ng/ml. Patients on argatroban did not generate immunoglobulin IgG reacting towards lepirudin in contrast to both patients on lepirudin who developed anti-lepirudin antibodies. Both treatments were well tolerated. Despite the low number of patients argatroban seems to lead to a more stable anticoagulant response than lepirudin resulting in a lower variability of the dosage for prophylaxis or treatment of thromboembolism of patients with a history of HIT and lepirudin antibodies. An erratum to this article can be found at .     

Predictive factors for thrombosis and major bleeding in an observational study in 181 patients with heparin-induced thrombocytopenia treated with lepirudin

The antithrombotic efficacy of lepirudin in patients with heparin-induced thrombocytopenia (HIT) is compromised by an increased risk for bleeding. A retrospective observational analysis in 181 patients (median age, 67 years) with confirmed HIT treated in routine practice with lepirudin was performed to identify predictive factors for thrombotic and bleeding complications. Lepirudin was administered at a mean (+/- SD) dose of 0.06 +/- 0.04 mg/kg/h (compared with a recommended initial dose of 0.15 mg/kg/h). Mean activated partial thromboplastin time was greater than 1.5 times baseline value in 99.4% of patients. Median treatment duration was 7.7 days. Until discharge from the hospital, 13.8% and 20.4% of patients experienced a thrombotic or a major bleeding event, respectively. On multivariate analysis, mean lepirudin dose was not a significant predictive factor for thrombosis. In contrast, mean lepirudin dose greater than 0.07 mg/kg/h, long duration of lepirudin treatment, and moderate to severe renal impairment were significant positive factors for major bleeding. Overall, these results suggest that the recommended dose of lepirudin in patients with HIT is too high; the use of reduced doses may be safer with regard to bleeding risk and does not compromise antithrombotic efficacy.     

Antihirudin antibodies in patients with heparin-induced thrombocytopenia treated with lepirudin: incidence, effects on aPTT, and clinical relevance

Hirudin, a potent and specific thrombin inhibitor, is a protein of nonhuman origin and therefore potentially immunogenic. The primary objectives of this investigation were to determine the incidence of antihirudin antibodies (ahir-ab) in patients with heparin-induced thrombocytopenia (HIT) who received lepirudin as parenteral anticoagulation and to determine the incidence of death, limb amputation, new thromboembolic complications (TECs), and major hemorrhage in patients who had ahir-ab, compared with patients who were ahir-ab negative. The investigation used data from 2 prospective multicenter studies with the same study protocol, in which HIT patients received 1 of 4 intravenous lepirudin dosage regimens. The treatment duration was 2 to 10 days. Ahir-ab were determined by a newly developed enzyme-linked immunosorbent assay (ELISA). Eighty-seven of 196 evaluable patients (44.4%) had ahir-ab of the IgG class. Development of ahir-ab was dependent on the duration of treatment (ahir-ab-positive patients 18.6 days vs ahir-ab-negative patients 11.8 days; P =.0001). Fewer ahir-ab-positive than ahir-ab-negative patients died (P =.001). Ahir-ab did not cause an increase in limb amputation (P =.765), new TECs (P >.99), or major bleedings (P =.549). In 23 of 51 (45.1%) evaluable patients in whom ahir-ab developed during treatment with lepirudin ( = 12% of all lepirudin treated patients), the ahir-ab enhanced the anticoagulatory effect of lepirudin. Ahir-ab are frequent in patients treated with lepirudin for more than 5 days. Ahir-ab are the first example for a drug-induced immune response causing enhanced activity of a drug. Therefore, during prolonged treatment with lepirudin, anticoagulatory activity should be monitored daily to avoid bleeding complications.     

Percutaneous interventions in patients with immune-mediated heparin-induced thrombocytopenia

The use of unfractionated heparin, the traditional antithrombotic agent during percutaneous coronary interventions (PCI), is associated with the risk of heparin-induced thrombocytopenia, a rare but often fatal clinical condition. This article focuses on several issues related to heparin-induced immune-mediated thrombocytopenia (HIT, type II) and alternative modes of periprocedural anticoagulation in patients with suspected or known HIT. The hypercoagulable state characterizing HIT, along with mechanical plaque disruption resulting from PCI place patients with HIT at particular risk of thrombosis during PCI. Given that a diagnosis of HIT precludes any further use of heparin, other treatment modalities are essential. Direct thrombin inhibitors are the drugs of choice in this challenging situation. These agents offer several advantages as anticoagulants for patients with HIT: (1) the ability to inhibit both thrombin that is bound to fibrin (clot-bound thrombin) and fluid-phase free thrombin; (2) rapid achievement of steady state; and (3) no cross-reactivity with HIT antibodies. Recent data on the use of bivalirudin, lepirudin, and argatroban in the setting of PCI in patients with HIT are encouraging. Optimal dosing regimens for argatroban, lepirudin, and bivalirudin should be further established in PCI patients.     

Nierenersatztherapie mittels SLEDD

For intensive care unit patients with acute renal failure, a new dialysis process called extended daily dialysis (EDD) or slow low-efficient daily dialysis (SLEDD), a so-called hybrid process, is an increasingly popular renal replacement treatment that combines the advantages of intermittent dialysis and continuous renal replacement therapy. In contrast to intermittent dialysis, the reduced rate of ultrafiltration results in better hemodynamic stability, while low-efficiency solute removal minimizes solute disequilibrium. Moreover, the daily costs can be reduced since dialysis fluid is less expensive with SLEDD than with application of ready-to-use fluid bags in CRRT. In the present studies, anticoagulation requirements were less for patients treated with SLEDD using the Genius system compared with CRRT. SLEDD combines high efficiency with good cardiovascular stability. Prospective studies directly comparing SLEDD to CRRT will help define the exact role for SLEDD in the critical care setting.     

The use of ecarin chromogenic assay and prothrombinase induced clotting time in the monitoring of lepirudin for the treatment of heparin-induced thrombocytopenia

Lepirudin (r-hirudin) is one of the two alternative anticoagulants licensed to treat patients with heparin-induced thrombocytopenia (HIT). Manufacturer's guidelines state that lepirudin should be monitored using the activated partial thromboplastin time (APTT) ratio. However, several studies have demonstrated a plateau effect of higher concentrations of lepirudin on APTT ratios and variable results when comparing different APTT reagents. This study compares APTT ratios (using two different APTT reagents) with two other commercially available methods for directly quantifying plasma lepirudin levels: ecarin chromogenic assay and prothrombinase-induced clotting time in 95 samples from five patients receiving lepirudin anticoagulation for HIT.     

The management of heparin-induced thrombocytopenia

The Haemostasis and Thrombosis Task Force of the British Committee for Standards in Haematology has produced a concise practical guideline to highlight the key issues in the management of heparin-induced thrombocytopenia (HIT) for the practicing physician in the UK. The guideline is evidence-based and levels of evidence are included in the body of the article. All patients who are to receive heparin of any sort should have a platelet count on the day of starting treatment. For patients who have been exposed to heparin in the last 100 d, a baseline platelet count and a platelet count 24 h after starting heparin should be obtained. For all patients receiving unfractionated heparin (UFH), alternate day platelet counts should be performed from days 4 to 14. For surgical and medical patients receiving low-molecular-weight heparin (LMWH) platelet counts should be performed every 2-4 d from days 4 to 14. Obstetric patients receiving treatment doses of LMWH should have platelet counts performed every 2-4 d from days 4 to 14. Obstetric patients receiving prophylactic LMWH are at low risk and do not need routine platelet monitoring. If the platelet count falls by 50% or more, or falls below the laboratory normal range and/or the patient develops new thrombosis or skin allergy between days 4 and 14 of heparin administration HIT should be considered and a clinical assessment made. If the pretest probability of HIT is high, heparin should be stopped and an alternative anticoagulant started at full dosage unless there are significant contraindications while laboratory tests are performed. Platelet activation assays using washed platelets have a higher sensitivity than platelet aggregation assays but are technically demanding and their use should be restricted to laboratories experienced in the technique. Non-expert laboratories should use an antigen-based assay of high sensitivity. Only IgG class antibodies need to be measured. Useful information is gained by reporting the actual optical density, inhibition by high concentrations of heparin, and the cut-off value for a positive test rather than simply reporting the test as positive or negative. In making a diagnosis of HIT the clinician's estimate of the pretest probability of HIT together with the type of assay used and its quantitative result (enzyme-linked immunosorbent assay, ELISA, only) should be used to determine the overall probability of HIT. Clinical decisions should be made following consideration of the risks and benefits of treatment with an alternative anticoagulant. For patients with strongly suspected or confirmed HIT, heparin should be stopped and full-dose anticoagulation with an alternative, such as lepirudin or danaparoid, commenced (in the absence of a significant contraindication). Warfarin should not be used until the platelet count has recovered. When introduced in combination with warfarin, an alternative anticoagulant must be continued until the International Normalised Ratio (INR) is therapeutic for two consecutive days. Platelets should not be given for prophylaxis. Lepirudin, at doses adjusted to achieve an activated partial thromboplastin time (APTT) ratio of 1.5-2.5, reduces the risk of reaching the composite endpoint of limb amputation, death or new thrombosis in patients with HIT and HIT with thrombosis (HITT). The risk of major haemorrhage is directly related to the APTT ratio, lepirudin levels and serum creatinine levels. The patient's renal function needs to be taken into careful consideration before treatment with lepirudin is commenced. Severe anaphylaxis occurs rarely in recipients of lepirudin and is more common in previously exposed patients. Danaparoid in a high-dose regimen is equivalent to lepirudin in the treatment of HIT and HITT. Danaparoid at prophylactic doses is not recommended for the treatment of HIT or HITT. Patients with previous HIT who are antibody negative (usually so after >100 d) who require cardiac surgery should receive intraoperative UFH in preference to other anticoagulants that are less validated for this purpose. Pre- and postoperative anticoagulation should be with an anticoagulant other than UFH or LMWH. Patients with recent or active HIT should have the need for surgery reviewed and delayed until the patient is antibody negative if possible. They should then proceed as above. If deemed appropriate early surgery should be carried out with an alternative anticoagulant. We recommend discussion of these complex cases requiring surgery with an experienced centre. The diagnosis must be clearly recorded in the patient's medical record.     

The use of direct thrombin inhibitors in cardiovascular surgery in patients with heparin-induced thrombocytopenia

One of the most important adverse drug reactions that physicians encounter is the life- and limb-threatening prothrombotic syndrome known as heparin-induced thrombocytopenia (HIT). Unfractionated heparin (UFH), administered during cardiopulmonary bypass (CPB), is highly immunogenic. Heparin-dependent antibodies can develop in 25 to 50% of UFH-treated cardiac surgery patients within 5 to 10 days. These antibodies can activate platelets and are considered the causative agents of HIT. HIT is a relatively common complication, occurring in 1 to 3% of cardiovascular surgery patients when UFH administration is continued postoperatively. It is strongly associated with new thromboembolic events leading to limb amputation and death. In acute or recent (< 100 days) HIT, alternative anticoagulatory regimens are needed during CPB surgery for prevention of HIT-related thrombosis. Treatment options for such patients now generally include the use of alternative anticoagulants such as lepirudin, bivalirudin, or danaparoid, as well as a combined treatment with platelet-function inhibitors and heparin. In patients with a history of HIT and no detectable antibodies, heparin is currently the safest approach for high-dose anticoagulation during CPB. Before and after surgery, however, alternative anticoagulants should be used. The risk of clinical HIT after heart surgery could potentially be reduced by using low-molecular-weight heparins for postsurgery anticoagulation.     

Hirudin-based anticoagulant strategies for patients with suspected heparin-induced thrombocytopenia undergoing percutaneous coronary interventions and bypass grafting

Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse drug reaction that is associated with thrombotic events of the venous and arterial circulatory systems stemming from an intense and well-characterized prothrombotic triad of platelet activation, coagulation cascade stimulation and vascular endothelial cell injury. Although heparin (or other sulfated mucopolysaccharide compound) cessation represents a vital first step in management, patients remain susceptible to life-threatening thrombosis for up to several weeks, providing a strong rationale for a 'proactive approach' to care that includes prompt initiation of an alternative anticoagulant strategy throughout the high-risk period. The importance of alternative options for anticoagulation is most evident in clinical situations wherein treatment is a recognized standard of care and prerequisite for an optimal outcome. The following review highlights the use of recombinant hirudin (lepirudin) among patients with suspected HIT requiring precutaneous coronary interventions (PCI) and coronary arterial bypass grafting.     

局部枸橼酸抗凝在肝衰竭患者连续性肾脏替代治疗中的应用

体外抗凝是连续性肾脏替代治疗(CRRT)的一项关键技术,肝素曾是CRRT首选的抗凝剂,但由于出血风险高,临床使用受限。枸橼酸作为一种新型局部抗凝剂,近年来受到越来越多的关注和推荐,但对于肝衰竭患者的应用一直存在争议。通过阅读近年来国内外相关文献,就局部枸橼酸抗凝在肝衰竭患者中的代谢特点、监测方法及其在CRRT应用中的安全性进行综述。     

Combination platelet glycoprotein IIb/IIIa receptor and lepirudin administration during percutaneous coronary intervention in patients with heparin-induced thrombocytopenia.

We evaluated a combination therapy using glycoprotein IIb/IIIa receptor antagonism and direct thrombin inhibition in nine patients with heparin-induced thrombocytopenia (HIT) undergoing 10 percutaneous coronary interventions (PCIs). In selected patients with HIT, the combination of a direct thrombin inhibitor, lepirudin, and abciximab, tirofiban, or eptifibatide appears to be a safe and effective anticoagulation strategy for PCI.     

The clinical diagnosis of heparin-induced thrombocytopenia in patients receiving continuous renal replacement therapy

Background Thrombocytopenia is common in critically ill patients who receive continuous renal replacement therapy. Often, these patients receive heparin therapy and the diagnosis of heparin induced thrombocytopenia (HIT) is considered as a potential etiology. No data regarding the clinical diagnosis of HIT is available for patients receiving continuous renal replacement therapy. Patients and methods We performed a retrospective study of 29 consecutive patients who received CRRT in a medical-surgical intensive care unit (ICU) and determined trends in platelet counts following CRRT and the frequency of meeting platelet based clinical criteria for consideration of a HIT diagnosis. Results For patient exposures to CRRT concurrent with heparin, 54% met at least one clinical threshold for consideration of the diagnosis of HIT. In 31% of exposures, both a platelet count <100,000/mm³ and a >50% decrease from baseline were seen. In contrast, the majority (73–85%) of patients receiving CRRT had a low pre-test probability of HIT using the “4T’s” scoring system. Mean platelet counts while on CRRT concurrent with heparin were significantly lower than when patients received heparin alone (P < 0.02). Conclusions The clinical diagnosis of HIT in ICU patients initiating CRRT is challenging given the decrease in platelet counts seen following CRRT initiation in the majority of patients. A prospective study in this population is needed to optimize patient outcomes.     

Der intensivpflichtige Patient mit Lungenembolie oder arteriellem Gefäßnotfall

Acute pulmonary embolism requires ICU management only for patients with hemodynamic instability who need artificial ventilation, or for hemodynamically stable patients with significant right ventricular dysfunction. For both patient groups, echocardiography is the most relevant diagnostic method. The main therapeutic consideration is on systemic thrombolysis. It is indicated in almost all patients with hemodynamic instability but only in selected cases of right ventricular dysfunction. All other patients receive standard anticoagulation only. A second vascular emergency scenario is type 2 heparin-induced thrombocytopeniae (HIT II) which may cause venous as well as arterial complications. Alternative anticoagulation has to be established from the first moment of clinical suspicion. It has to be continued in a therapeutic dosage if HIT II is confirmed, and has to be stopped if the diagnosis is refuted. The latter case is by far more frequent. Regarding arterial occlusions (acute limb ischemia, acral gangrene, iatrogenic vascular trauma) hints are given for the management in the setting of intensive care.     

Lepirudin for prophylaxis of thrombosis in patients with acute isolated heparin-induced thrombocytopenia: an analysis of 3 prospective studies

This analysis of 3 prospective multicenter trials in patients with laboratory-confirmed acute heparin-induced thrombocytopenia (HIT) without clinically evident thromboembolic complications (TECs), isolated HIT, assessed the combined individual end points of death, new TECs, and limb amputation. Patients with the same inclusion criteria who did not receive lepirudin or danaparoid served as a contemporaneous control group. Ninety-one patients were treated with lepirudin (intravenous infusion 0.10 mg/kg/h, no bolus, activated partial thromboplastin time [aPTT]-adjusted to 1.5-2.5 times baseline) for a median of 11.0 days (range, 1-68 days). During the observation period (median 24 days), 13 (14.3%) deaths, 4 (4.4%) new TECs, 3 (3.3%) limb amputations (combined 18 [19.8%]), and 13 (14.3%) major bleeding events occurred. In comparison to the control group (N = 47), the combined end point (P = .0281) and new TECs (P = .02) were reduced, and major bleeding was not significantly different between groups (P = .5419). In renal impairment, lepirudin did not reach its steady state within 4 hours, and additional monitoring every 4 hours after start of lepirudin until steady state is reached is recommended. Lepirudin seems to be effective in patients with isolated HIT. Dose reductions in renal impairment are important. Keeping the aPTT in the range corresponding to 600 to 700 microg/L lepirudin during treatment may minimize bleeding complications.     

Heparins, low-molecular-weight heparins, and pentasaccharides

Elderly patients require special consideration when administered anticoagulants because of age-related alterations in renal function, protein binding, and increased bleeding risk. Unfractionated heparin can be used in most patients but difficulties with dosing and monitoring often lead to inadequate anticoagulation. Low-molecular-weight heparin has more predictable pharmacokinetics than conventional heparin, but requires dose adjustments in renal impairment and obesity. Fondaparinux is a synthetic pentasaccharide that is being used increasingly for both treatment and prophylaxis of venous thromboembolism. The immune-mediated form of heparin-induced thrombocytopenia is a syndrome with thrombocytopenia or thrombosis in the setting of heparin use. Heparin-induced thrombocytopenia must be identified early, and treated with argatroban or lepirudin to avoid life-threatening complications.     

Continuous renal replacement therapy after heart transplantation

BACKGROUND: Renal failure following heart transplantation carries a poor prognosis. The objectives of this study were to determine risk factors for renal failure requiring continuous renal replacement therapy (CRRT), to describe the management strategies regarding immunosuppressive therapy and to examine the short-term prognosis. METHODS: Fifty-six patients who underwent heart transplantation from 1998 to 2002 at the Montreal Heart Institute were retrospectively analyzed. RESULTS: Six of 56 patients (11%) underwent CRRT after heart transplantation. Patients who underwent CRRT had lower preoperative creatinine clearance than those who did not (median 44 versus 59 mL/min, P=0.04) and lower first two-week postoperative creatinine clearance (median 23 versus 42 mL/min, P<0.01) compared with patients without CRRT. The total duration of CRRT ranged between two and 60 days (median 15 days). Cyclosporine was withheld for 12 days versus two days (P<0.01) and the time to achieve therapeutic levels of cyclosporine averaged 18 days versus nine days (P=0.01) among CRRT versus non-CRRT patients. Patients were administered thymoglobulin or basiliximab during cyclosporine withholding. The time to discharge from hospital after transplantation was longer in patients with CRRT (median 47 days versus 17 days, P<0.01). There was no mortality at three months in the CRRT group. CONCLUSION: Creatinine clearance is an important predictor of renal failure requiring renal replacement therapy. Although renal failure remains a serious complication after transplantation, the use of CRRT and antilymphocyte agents during cyclosporine A withholding is associated with a favourable short-term prognosis following heart transplantation.