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Argatroban and renal replacement therapy in a morbidly obese patient with heparin-induced thrombocytopenia: A case report
Thrombosis Research 126 (2010) e141–e143
Contents lists available at ScienceDirect
Thrombosis Research j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / t h r o m r e s
Letter to the Editors-in-Chief Argatroban and renal replacement therapy in a morbidly obese patient with heparin-induced thrombocytopenia: A case report
Keywords: Renal replacement therapy Reparin induced thrombocytopenia Obesity Argatroban
Continuous veno-venous hemofiltration (CVVH) is widely used for renal replacement therapy (RRT) in intensive care units (ICUs). However, because patients undergoing CVVH often receive unfractionated heparin (UFH), there is a risk of Heparin-Induced Thrombocytopenia (HIT) and also of repeated hemofilter thrombosis [1,2]. Administration of a reversible direct thrombin inhibitor, such as argatroban or lepirudin, or of the heparinoid, danaparoid, is an alternative anti-coagulation strategy for RRT in patients with HIT. However, information on the use of argatroban in obese patients is relatively scarce. We report the case of a morbidly obese patient who received dose-adjusted argatroban for RRT with monitoring of anti-IIa activity.
Case report A 37-year-old morbidly obese man (157 kg, BMI 53 kg.m2) with no significant medical history was admitted to our ICU after emergency resection of an infarcted bowel secondary to an incarcerated abdominal hernia. The patient was suffering from septic shock, acute respiratory distress syndrom, and acute renal failure. Continuous veno-venous hemofiltration (CVVH) using the MultiFiltrate system with a polysulfone filter ultraflux (AV600S, Fresenius Medical Care, Germany) was started (blood flow, 250-300 mL/min; ultrafiltrate flow, 35 mL/kg/hr [3] (one third prefilter, two thirds post-filter); loading UFH dose, 10 000 IU; maintenance dose, 8 IU/kg/hr). Repeated thrombosis of the hemofiltration filters occurred 14 days later, well before the expected 24-hour filter lifespan had expired. The activated partial thromboplastin time (aPTT) ratio was unstable (from N3 to 1). The UFH dose was gradually increased but with no improvement in filter life. Acquired antithrombin (AT) deficiency was suspected (AT level, 53%). Activity was restored (173%) by administration of a 3000 IU bolus of AT but hemofilter thrombosis persisted. The patient's blood count was normal except for moderate thrombocytopenia (99.109/L versus 239.109/L just before surgery). In the absence of any other sign of disseminated intravascular coagulation (e.g. fibrinogen increase to 7 g/l), we suspected HIT. Anti-PF4/ heparin antibodies were positive in the rapid test Gel agglutination assay (ID-PaGIA Heparin/PF4 antibody, DIAMED, Chambly, France) and ELISA (Diagnostica-Stago, Asnière-sur-Seine, France) (optical density N1.0 IU on two consecutive plasma samples). However, the serotonin release assay, the gold standard test for HIT, was negative. On the following day, deep vein thrombosis and pulmonary embolism 0049-3848/$ – see front matter © 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.thromres.2009.12.018
were diagnosed by Doppler compression ultrasound and computed tomography, respectively. The Four T-Score [4], though not validated in ICU patients, increased from 4 points (thrombocytopenia with 50% fall or nadir of 20 to 100.109/L = 2 points; consistent with fall on days 5–10 but not clear = 1 point; other possible causes for thrombocytopenia = 1 point) to 6 points (confirmed new thrombosis = 2 points). All heparin was stopped and replaced by danaparoid (Orgaran®) (loading dose, 4000 IU anti-Xa; maintenance dose, 600 IU/hr anti-Xa). After two days treatment, however, the drug accumulated and the patient was overdosed (specific anti-Xa activity N1 IU/mL). The choice of an alternative drug was difficult: Europe was experiencing a shortage in supply of danaparoid, lepirudin would also carry a risk of drug accumulation and bleeding because of its renal elimination [5], and argatroban and bilavirudin had not yet received marketing approval for HIT in France. The French health authorities finally granted authorization for temporary argatroban use. In the absence of data in obese patients, the infusion was started at 0.5 μg/kg/ min, i.e. half the dose used in chronic RRT [6,7] and a quarter of the dose recommended by the manufacturer. Despite this low dose, excessive anticoagulation was observed. Specific anti-IIa activity was 1.2 μg/mL (Hemoclot thrombin inhibitors, Hyphen BioMed, Neuvillesur-Oise, France) and the aPTT ratio was 2.0 (TriniCLOT automated APTT, Trinity-Biotech, Champigny sur Marne France). As the patient had not yet eliminated danaparoid (residual anti-Xa activity, 0.5-1 IU/ mL), the argatroban dose was reduced to 0.4 μg/kg/min. This dose maintained coagulation parameters within the targeted range (anti-IIa activity, 0.4-0.8 μg/mL). Five days after starting argatroban, the dose was increased to 0.8 μg/kg/min to maintain correct anticoagulation. Argatroban was infused for 23 consecutive days. The CVVH filter lifespan increased and, 5 days after argatroban initiation, platelet count returned to normal (215.109/L). Standard liver function parameters did not change significantly during this time. No bleeding occurred. CVVH was stopped and the argatroban infusion (0.8 μg/kg/ min) was continued. An oral vitamin K antagonist (VKA) (warfarin, Coumadin®) was progressively introduced (initial dose, 5 mg). Since a therapeutic dose of argatroban prolongs prothrombin time and increases the International Normalized Ratio (INR), we decided to monitor INR and coagulation factors VII, X and II using chronometric assays. However, argatroban interfered with the assay of vitamin Kdependent factors even at low plasma dilutions. (The chromogenic factor X assay recommended for the management of argatroban/VKA overlap by the American College of Clinical Pharmacology guidelines [8] was not available in our hospital.) Argatroban was discontinued when factor II was around 30% and factor VII 25%. Four hours after warfarin administration, the INR, which was 3.7 on argatroban treatment, fell to 2.3. The patient left our ICU 5 days later and was discharged from hospital after one month with a 6-month VKA prescription. No thrombophilia was detected at discharge. Discussion The incidence of HIT in ICUs is 0.3% to 0.5% [1]. The diagnosis of HIT in our patient was not straightforward as the result of the functional
e142
Letter to the Editors-in-Chief
Fig. 1. Coagulation monitoring during 37 consecutive days before and during argatroban therapy. (♦) represent aPTT ratio with TriniCLOT automated APTT and (▲) argatroban concentration in μg/ml measured with Hemoclot thrombin inhibitors (Hypen BioMed, Neuville- sur-Oise, France). (X) show evolution of platelets count (109/L). 55 consecutive measurements of biological parameters are presented.
diagnostic assay for HIT – the serotonin release assay – was negative. This negative result could, however, have been due to a technical limitation of the assay as platelets from some donors are not readily activated by HIT sera [9]. In a recent study, 24 of 51 patients with suspected HIT (i.e. with a high-probability 4 T score) were positive for anti-PF4/heparin antibodies but negative for the platelet activation test [10]. Unfortunately, the study gave no data for serotonin release. The evidence for HIT was as follows: thrombocytopenia, a high pretest probability score, positive anti-PF4/heparin antibodies, repeated hemofilter thrombosis, bilateral deep vein thrombosis and pulmonary embolism. Hemofiltration filter clogging has been associated with anti-PF4/heparin antibodies without the typical fall in platelet count being observed [1,2]. The patient's AT level was within the normal range and there was no catheter dysfunction. Substitution of heparin by a dose of 0.4 to 0.8 μg/kg/min argatroban restored CVVH duration and efficiency, improved the patient's condition, and normalized platelet count. Our case report suggests that the usually recommended dose of argatroban (2 μg/kg/min) may be too high in critically ill patients with septic shock or multiple organ dysfunction. Shock-induced reduced liver perfusion often impairs hepatic clearance. The elimination halflife of argatroban (39-51 minutes [10–12]) was therefore probably increased. Although there is no antidote for argatroban, coagulation measures such as the aPTT typically return to baseline 2-4 hours after the infusion is discontinued. Dose adjustments are not usually recommended in renal failure and RRT as its dialytic clearance by high flux membranes is clinically insignificant [13,14]. However, since critical illness prognostic scores (APACHE II, SAPS II) have been shown to be correlated to the argatroban maintenance infusion rate [7], we adjusted dose in our patient first downward to allow elimination of an earlier drug, then upward when his condition improved. According to recent publications, argatroban doses of 0.5 to 1.2 μg/ kg/min achieve therapeutic aPTTs, and not just in critically ill patients [15]. These studies did not all monitor argatroban plasma level. To monitor argatroban, we have found, like others [16], that anti-IIa activity is a simple, robust additional coagulation measure. In our laboratory, a stable aPTT ratio of about 2.0 was correlated with an
anti-IIa activity that did not exceed 0.8 μg/mL (mean concentration, 0.7 μg/mL over 23 days) (Fig. 1), in agreement with the results of an in-vitro study [17]. Our report is the first, to our knowledge, to address the use of argatroban for CVVH in a morbidly obese patient. Argatroban doses were calculated using total body weight and not dry weight and provided adequate control of coagulation parameters. According to a retrospective multicenter study, argatroban dosing requirements and aPTT responses are similar in non-obese and obese patients (BMI up to 51 kg/m²) [18]. In addition, in a series of 75 obese patients undergoing percutaneous coronary intervention, no association was found between BMI and the Activated Clotting Time (ACT) response [19]. These results thus support the use of argatroban doses adjusted to actual body weight with no need to adjust additionally for obesity. On the other hand, in one morbidly obese patient, aPTT was prolonged for several days after argatroban discontinuation suggesting that obesity might slow down reversal of the anticoagulant effect [20]. We did not confirm this. Four hours after argatroban discontinuation, coagulation parameters but not the INR had returned to normal. We thus confirm an earlier observation with higher argatroban doses in obese patients where the ACT began to decrease immediately after argatroban was discontinued [19]. In conclusion, the use of argatroban in CVVH patients needs close monitoring of coagulation parameters. In addition to aPTT ratio, antiIIa activity appears as an optimal test. This case points out that dosing of argatroban has to be adjusted in critically ill patients with dose reduction due to multi-organ dysfunction and without special concern for morbidly obese patients. Conflict of interest statement The authors have no conflict of interest. References [1] Selleng K, Warkentin TE, Greinacher A. Heparin-induced thrombocytopenia in intensive care patients. Crit Care Med 2007;35:1165–76.
Letter to the Editors-in-Chief [2] Lasocki S, Piednoir P, Ajzenberg N, et al. Anti-PF4/heparin antibodies associated with repeated hemofiltration-filter clotting: a retrospective study. Crit Care 2008;12:R84. [3] Ronco C, Bellomo R, Homel P, Brendolan A, Dan M, Piccinni P, et al. Effects of different doses in continuous veno-venous haemofiltration on outcomes of acute renal failure: a prospective randomised trial. Lancet 2000;356:26–30. [4] Warkentin TE. Heparin-induced thrombocytopenia: diagnosis and management. Circulation 2004;110:454–8. [5] Tschudi M, Lämmle B, Alberio L. Dosing lepirudin in patients with heparin-induced thrombocytopenia and normal or impaired renal function: a single-center experience with 68 patients. Blood 2009;113:2402–9. [6] Koster A, Hentschel T, Groman T, et al. Argatroban anticoagulation for renal replacement therapy in patients with heparin-induced thrombocytopenia after cardiovascular surgery. J Thorac Cardiovasc Surg 2007;133:1376–7. [7] Link A, Girndt M, Selejan S, et al. Argatroban for anticoagulation in continuous renal replacement therapy. Crit Care Med 2009;37:105–10. [8] Hirsh J, Bauer KA, Donati MB, et al. Parenteral anticoagulants: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008;133:141S–59S. [9] Warkentin TE. Determinants of donor platelet variability when testing for HIT. J Lab Clin Med 1992;120:371–9. [10] Bakchoul T, Giptner A, Najaoui A, Bein G, Santoso S, Sachs UJ. Prospective evaluation of PF4/heparin immunoassays for the diagnosis of heparin-induced thrombocytopenia. J Thromb Haemost 2009;7:1260–5. [11] Lewis BE, Wallis DE, Berkowitz SD, et al. Argatroban anticoagulant therapy in patients with heparin-induced thrombocytopenia. Circulation 2001;103:1838–43. [12] Lewis BE, Wallis DE, Leya F, et al. Argatroban anticoagulation in patients with heparin-induced thrombocytopenia. Arch Intern Med 2003;163:1849–56. [13] Tang IY, Cox DS, Patel K, et al. Argatroban and renal replacement therapy in patients with heparin-induced thrombocytopenia. Ann Pharmacother 2005;39:231–6. [14] Murray PT, Reddy BV, Grossman EJ, et al. A prospective comparison of three argatroban treatment regimens during hemodialysis in end-stage renal disease. Kidney Int 2004;66:2446–53. [15] Warkentin TE, Greinacher A, Koster A, et al. Treatment and prevention of heparininduced thrombocytopenia: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008;133:340S–80S. [16] Love JE, Ferrell C, Chandler WL. Monitoring direct thrombin inhibitors with a plasma diluted thrombin time. Thromb Haemost 2007;98:234–42. [17] Francis JL, Hursting MJ. Effect of argatroban on the activated partial thromboplastin time: a comparison of 21 commercial reagents. Blood Coagul Fibrinolysis 2005;16:251–7.
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[18] Rice L, Hursting MJ, Baillie GM, et al. Argatroban anticoagulation in obese versus nonobese patients: implications for treating heparin-induced thrombocytopenia. J Clin Pharmacol 2007;47:1028–34. [19] Hursting MJ, Jang IK. Effect of body mass index on Argatroban therapy during percutaneous coronary intervention. J Thromb Thrombolysis 2008;25:273–9. [20] Shapiro NL, Durr EA, Krueger CD. Prolonged anticoagulation after discontinuation of argatroban and warfarin therapy in an obese patient with heparin-induced thrombocytopenia. Pharmacotherapy 2006;26:1806–10.
Anne Godier⁎ Marine De Mesmay Xavier Bécanne Marion Parisot Rémy Gauzit Charles-Marc Samama Department of Anaesthesiology and Intensive Care, Hôtel-Dieu, Paris Descartes University, AP-HP, Paris, France ⁎Corresponding author. Department of Anaesthesiology and Intensive `Care, Hôtel-Dieu, Paris Descartes University, AP-HP, 1, place du Parvis de Notre-Dame, 75004 Paris, France. Tel.: + 33 1 42 34 83 09; fax: + 33 1 42 34 89 60. E-mail address: [email protected] (A. Godier). Claire Flaujac Marie-Hélène Horellou Department of Biological Haematology, Hôtel-Dieu, Paris Descartes University, AP-HP, Paris, France 16 August 2009
Contents lists available at ScienceDirect
Thrombosis Research j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / t h r o m r e s
Letter to the Editors-in-Chief Argatroban and renal replacement therapy in a morbidly obese patient with heparin-induced thrombocytopenia: A case report
Keywords: Renal replacement therapy Reparin induced thrombocytopenia Obesity Argatroban
Continuous veno-venous hemofiltration (CVVH) is widely used for renal replacement therapy (RRT) in intensive care units (ICUs). However, because patients undergoing CVVH often receive unfractionated heparin (UFH), there is a risk of Heparin-Induced Thrombocytopenia (HIT) and also of repeated hemofilter thrombosis [1,2]. Administration of a reversible direct thrombin inhibitor, such as argatroban or lepirudin, or of the heparinoid, danaparoid, is an alternative anti-coagulation strategy for RRT in patients with HIT. However, information on the use of argatroban in obese patients is relatively scarce. We report the case of a morbidly obese patient who received dose-adjusted argatroban for RRT with monitoring of anti-IIa activity.
Case report A 37-year-old morbidly obese man (157 kg, BMI 53 kg.m2) with no significant medical history was admitted to our ICU after emergency resection of an infarcted bowel secondary to an incarcerated abdominal hernia. The patient was suffering from septic shock, acute respiratory distress syndrom, and acute renal failure. Continuous veno-venous hemofiltration (CVVH) using the MultiFiltrate system with a polysulfone filter ultraflux (AV600S, Fresenius Medical Care, Germany) was started (blood flow, 250-300 mL/min; ultrafiltrate flow, 35 mL/kg/hr [3] (one third prefilter, two thirds post-filter); loading UFH dose, 10 000 IU; maintenance dose, 8 IU/kg/hr). Repeated thrombosis of the hemofiltration filters occurred 14 days later, well before the expected 24-hour filter lifespan had expired. The activated partial thromboplastin time (aPTT) ratio was unstable (from N3 to 1). The UFH dose was gradually increased but with no improvement in filter life. Acquired antithrombin (AT) deficiency was suspected (AT level, 53%). Activity was restored (173%) by administration of a 3000 IU bolus of AT but hemofilter thrombosis persisted. The patient's blood count was normal except for moderate thrombocytopenia (99.109/L versus 239.109/L just before surgery). In the absence of any other sign of disseminated intravascular coagulation (e.g. fibrinogen increase to 7 g/l), we suspected HIT. Anti-PF4/ heparin antibodies were positive in the rapid test Gel agglutination assay (ID-PaGIA Heparin/PF4 antibody, DIAMED, Chambly, France) and ELISA (Diagnostica-Stago, Asnière-sur-Seine, France) (optical density N1.0 IU on two consecutive plasma samples). However, the serotonin release assay, the gold standard test for HIT, was negative. On the following day, deep vein thrombosis and pulmonary embolism 0049-3848/$ – see front matter © 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.thromres.2009.12.018
were diagnosed by Doppler compression ultrasound and computed tomography, respectively. The Four T-Score [4], though not validated in ICU patients, increased from 4 points (thrombocytopenia with 50% fall or nadir of 20 to 100.109/L = 2 points; consistent with fall on days 5–10 but not clear = 1 point; other possible causes for thrombocytopenia = 1 point) to 6 points (confirmed new thrombosis = 2 points). All heparin was stopped and replaced by danaparoid (Orgaran®) (loading dose, 4000 IU anti-Xa; maintenance dose, 600 IU/hr anti-Xa). After two days treatment, however, the drug accumulated and the patient was overdosed (specific anti-Xa activity N1 IU/mL). The choice of an alternative drug was difficult: Europe was experiencing a shortage in supply of danaparoid, lepirudin would also carry a risk of drug accumulation and bleeding because of its renal elimination [5], and argatroban and bilavirudin had not yet received marketing approval for HIT in France. The French health authorities finally granted authorization for temporary argatroban use. In the absence of data in obese patients, the infusion was started at 0.5 μg/kg/ min, i.e. half the dose used in chronic RRT [6,7] and a quarter of the dose recommended by the manufacturer. Despite this low dose, excessive anticoagulation was observed. Specific anti-IIa activity was 1.2 μg/mL (Hemoclot thrombin inhibitors, Hyphen BioMed, Neuvillesur-Oise, France) and the aPTT ratio was 2.0 (TriniCLOT automated APTT, Trinity-Biotech, Champigny sur Marne France). As the patient had not yet eliminated danaparoid (residual anti-Xa activity, 0.5-1 IU/ mL), the argatroban dose was reduced to 0.4 μg/kg/min. This dose maintained coagulation parameters within the targeted range (anti-IIa activity, 0.4-0.8 μg/mL). Five days after starting argatroban, the dose was increased to 0.8 μg/kg/min to maintain correct anticoagulation. Argatroban was infused for 23 consecutive days. The CVVH filter lifespan increased and, 5 days after argatroban initiation, platelet count returned to normal (215.109/L). Standard liver function parameters did not change significantly during this time. No bleeding occurred. CVVH was stopped and the argatroban infusion (0.8 μg/kg/ min) was continued. An oral vitamin K antagonist (VKA) (warfarin, Coumadin®) was progressively introduced (initial dose, 5 mg). Since a therapeutic dose of argatroban prolongs prothrombin time and increases the International Normalized Ratio (INR), we decided to monitor INR and coagulation factors VII, X and II using chronometric assays. However, argatroban interfered with the assay of vitamin Kdependent factors even at low plasma dilutions. (The chromogenic factor X assay recommended for the management of argatroban/VKA overlap by the American College of Clinical Pharmacology guidelines [8] was not available in our hospital.) Argatroban was discontinued when factor II was around 30% and factor VII 25%. Four hours after warfarin administration, the INR, which was 3.7 on argatroban treatment, fell to 2.3. The patient left our ICU 5 days later and was discharged from hospital after one month with a 6-month VKA prescription. No thrombophilia was detected at discharge. Discussion The incidence of HIT in ICUs is 0.3% to 0.5% [1]. The diagnosis of HIT in our patient was not straightforward as the result of the functional
e142
Letter to the Editors-in-Chief
Fig. 1. Coagulation monitoring during 37 consecutive days before and during argatroban therapy. (♦) represent aPTT ratio with TriniCLOT automated APTT and (▲) argatroban concentration in μg/ml measured with Hemoclot thrombin inhibitors (Hypen BioMed, Neuville- sur-Oise, France). (X) show evolution of platelets count (109/L). 55 consecutive measurements of biological parameters are presented.
diagnostic assay for HIT – the serotonin release assay – was negative. This negative result could, however, have been due to a technical limitation of the assay as platelets from some donors are not readily activated by HIT sera [9]. In a recent study, 24 of 51 patients with suspected HIT (i.e. with a high-probability 4 T score) were positive for anti-PF4/heparin antibodies but negative for the platelet activation test [10]. Unfortunately, the study gave no data for serotonin release. The evidence for HIT was as follows: thrombocytopenia, a high pretest probability score, positive anti-PF4/heparin antibodies, repeated hemofilter thrombosis, bilateral deep vein thrombosis and pulmonary embolism. Hemofiltration filter clogging has been associated with anti-PF4/heparin antibodies without the typical fall in platelet count being observed [1,2]. The patient's AT level was within the normal range and there was no catheter dysfunction. Substitution of heparin by a dose of 0.4 to 0.8 μg/kg/min argatroban restored CVVH duration and efficiency, improved the patient's condition, and normalized platelet count. Our case report suggests that the usually recommended dose of argatroban (2 μg/kg/min) may be too high in critically ill patients with septic shock or multiple organ dysfunction. Shock-induced reduced liver perfusion often impairs hepatic clearance. The elimination halflife of argatroban (39-51 minutes [10–12]) was therefore probably increased. Although there is no antidote for argatroban, coagulation measures such as the aPTT typically return to baseline 2-4 hours after the infusion is discontinued. Dose adjustments are not usually recommended in renal failure and RRT as its dialytic clearance by high flux membranes is clinically insignificant [13,14]. However, since critical illness prognostic scores (APACHE II, SAPS II) have been shown to be correlated to the argatroban maintenance infusion rate [7], we adjusted dose in our patient first downward to allow elimination of an earlier drug, then upward when his condition improved. According to recent publications, argatroban doses of 0.5 to 1.2 μg/ kg/min achieve therapeutic aPTTs, and not just in critically ill patients [15]. These studies did not all monitor argatroban plasma level. To monitor argatroban, we have found, like others [16], that anti-IIa activity is a simple, robust additional coagulation measure. In our laboratory, a stable aPTT ratio of about 2.0 was correlated with an
anti-IIa activity that did not exceed 0.8 μg/mL (mean concentration, 0.7 μg/mL over 23 days) (Fig. 1), in agreement with the results of an in-vitro study [17]. Our report is the first, to our knowledge, to address the use of argatroban for CVVH in a morbidly obese patient. Argatroban doses were calculated using total body weight and not dry weight and provided adequate control of coagulation parameters. According to a retrospective multicenter study, argatroban dosing requirements and aPTT responses are similar in non-obese and obese patients (BMI up to 51 kg/m²) [18]. In addition, in a series of 75 obese patients undergoing percutaneous coronary intervention, no association was found between BMI and the Activated Clotting Time (ACT) response [19]. These results thus support the use of argatroban doses adjusted to actual body weight with no need to adjust additionally for obesity. On the other hand, in one morbidly obese patient, aPTT was prolonged for several days after argatroban discontinuation suggesting that obesity might slow down reversal of the anticoagulant effect [20]. We did not confirm this. Four hours after argatroban discontinuation, coagulation parameters but not the INR had returned to normal. We thus confirm an earlier observation with higher argatroban doses in obese patients where the ACT began to decrease immediately after argatroban was discontinued [19]. In conclusion, the use of argatroban in CVVH patients needs close monitoring of coagulation parameters. In addition to aPTT ratio, antiIIa activity appears as an optimal test. This case points out that dosing of argatroban has to be adjusted in critically ill patients with dose reduction due to multi-organ dysfunction and without special concern for morbidly obese patients. Conflict of interest statement The authors have no conflict of interest. References [1] Selleng K, Warkentin TE, Greinacher A. Heparin-induced thrombocytopenia in intensive care patients. Crit Care Med 2007;35:1165–76.
Letter to the Editors-in-Chief [2] Lasocki S, Piednoir P, Ajzenberg N, et al. Anti-PF4/heparin antibodies associated with repeated hemofiltration-filter clotting: a retrospective study. Crit Care 2008;12:R84. [3] Ronco C, Bellomo R, Homel P, Brendolan A, Dan M, Piccinni P, et al. Effects of different doses in continuous veno-venous haemofiltration on outcomes of acute renal failure: a prospective randomised trial. Lancet 2000;356:26–30. [4] Warkentin TE. Heparin-induced thrombocytopenia: diagnosis and management. Circulation 2004;110:454–8. [5] Tschudi M, Lämmle B, Alberio L. Dosing lepirudin in patients with heparin-induced thrombocytopenia and normal or impaired renal function: a single-center experience with 68 patients. Blood 2009;113:2402–9. [6] Koster A, Hentschel T, Groman T, et al. Argatroban anticoagulation for renal replacement therapy in patients with heparin-induced thrombocytopenia after cardiovascular surgery. J Thorac Cardiovasc Surg 2007;133:1376–7. [7] Link A, Girndt M, Selejan S, et al. Argatroban for anticoagulation in continuous renal replacement therapy. Crit Care Med 2009;37:105–10. [8] Hirsh J, Bauer KA, Donati MB, et al. Parenteral anticoagulants: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008;133:141S–59S. [9] Warkentin TE. Determinants of donor platelet variability when testing for HIT. J Lab Clin Med 1992;120:371–9. [10] Bakchoul T, Giptner A, Najaoui A, Bein G, Santoso S, Sachs UJ. Prospective evaluation of PF4/heparin immunoassays for the diagnosis of heparin-induced thrombocytopenia. J Thromb Haemost 2009;7:1260–5. [11] Lewis BE, Wallis DE, Berkowitz SD, et al. Argatroban anticoagulant therapy in patients with heparin-induced thrombocytopenia. Circulation 2001;103:1838–43. [12] Lewis BE, Wallis DE, Leya F, et al. Argatroban anticoagulation in patients with heparin-induced thrombocytopenia. Arch Intern Med 2003;163:1849–56. [13] Tang IY, Cox DS, Patel K, et al. Argatroban and renal replacement therapy in patients with heparin-induced thrombocytopenia. Ann Pharmacother 2005;39:231–6. [14] Murray PT, Reddy BV, Grossman EJ, et al. A prospective comparison of three argatroban treatment regimens during hemodialysis in end-stage renal disease. Kidney Int 2004;66:2446–53. [15] Warkentin TE, Greinacher A, Koster A, et al. Treatment and prevention of heparininduced thrombocytopenia: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008;133:340S–80S. [16] Love JE, Ferrell C, Chandler WL. Monitoring direct thrombin inhibitors with a plasma diluted thrombin time. Thromb Haemost 2007;98:234–42. [17] Francis JL, Hursting MJ. Effect of argatroban on the activated partial thromboplastin time: a comparison of 21 commercial reagents. Blood Coagul Fibrinolysis 2005;16:251–7.
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[18] Rice L, Hursting MJ, Baillie GM, et al. Argatroban anticoagulation in obese versus nonobese patients: implications for treating heparin-induced thrombocytopenia. J Clin Pharmacol 2007;47:1028–34. [19] Hursting MJ, Jang IK. Effect of body mass index on Argatroban therapy during percutaneous coronary intervention. J Thromb Thrombolysis 2008;25:273–9. [20] Shapiro NL, Durr EA, Krueger CD. Prolonged anticoagulation after discontinuation of argatroban and warfarin therapy in an obese patient with heparin-induced thrombocytopenia. Pharmacotherapy 2006;26:1806–10.
Anne Godier⁎ Marine De Mesmay Xavier Bécanne Marion Parisot Rémy Gauzit Charles-Marc Samama Department of Anaesthesiology and Intensive Care, Hôtel-Dieu, Paris Descartes University, AP-HP, Paris, France ⁎Corresponding author. Department of Anaesthesiology and Intensive `Care, Hôtel-Dieu, Paris Descartes University, AP-HP, 1, place du Parvis de Notre-Dame, 75004 Paris, France. Tel.: + 33 1 42 34 83 09; fax: + 33 1 42 34 89 60. E-mail address: [email protected] (A. Godier). Claire Flaujac Marie-Hélène Horellou Department of Biological Haematology, Hôtel-Dieu, Paris Descartes University, AP-HP, Paris, France 16 August 2009