535361
research-article2014
AOPXXX10.1177/1060028014535361Annals of PharmacotherapyGrandvuillemin et al
Article
Unusual Case of HIT With Cardiac Arrest During Hemodialysis
Annals of Pharmacotherapy 1–4 © The Author(s) 2014 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1060028014535361 aop.sagepub.com
Aurélie Grandvuillemin, PharmD1, Gilbert Zanetta, MD2, Julien Perrin, MD3, Jean Amiral, MD4, Ismail Elalamy, MD5, and Emmanuel de Maistre, MD2
Abstract Objective: To report an unusual case of heparin-induced thrombocytopenia (HIT) with cardiac arrest during hemodialysis (HD). Case Summary: An 88-year-old man previously treated with HD under enoxaparin for 3 years presented with dizziness and cyanosis at the beginning of HD on 3 consecutive sessions. Even though the dialyzer membrane was changed, he presented with cardiac arrest, from which he recovered quickly. At the same time, the platelet count fell, and HIT was suspected. No thrombosis was found. Anti-PF4/H, IL8, and NAP2 antibodies were negative, but platelet aggregation tests and serotonin-release assay were positive. After implementing HD with danaparoid, the platelet count returned to normal, and the patient remained asymptomatic. Discussion: Given the clinical context (low-molecular-weight heparin), complications (cardiac arrest and no thrombosis), and timing (3 years), this was an unusual case of HIT. According to the Naranjo probability scale, the causality of enoxaparin was evaluated as probable. In most reported cases, time to onset was short, clotting occurred in the extracorporeal system, and biological tests, including ELISA (enzyme-linked immunosorbent assay) anti-PF4/heparin, were positive. We found no triggering factor in this case, and given the biological results, a new antigenic target may be involved. Conclusions: HIT must be considered when acute systemic reactions occur at the beginning of HD sessions, even after several years of HD and with no change of anticoagulant, including low-molecularweight heparin. The platelet count should be measured immediately after the reaction. The diagnosis is important because of possible cardiac arrest in this context. Keywords hemodialysis, heparin-induced thrombocytopenia, allergy
Introduction Heparin is the most commonly used extracorporeal anticoagulant for hemodialysis (HD), and heparin-induced thrombocytopenia (HIT) has been reported in this clinical context. This kind of adverse reaction may lead to thrombotic complications. In exceptional cases, acute systemic reactions can occur. According to published cases, the time to onset of these adverse reactions is usually short. We present a case of HIT that is unusual because of the clinical context, the complications, and timing.
Case Report An 88-year-old man had been treated with HD for 3 years. His main medical history included myocardial infarction, atrial fibrillation, and renal insufficiency. He had been treated with furosemide, vitamin K antagonist fluindione (with stable international normalized ratio [INR] between 2 and 3), atorvastatin, alfacalcidiol, cinacalcet, and ramipril.
He had undergone HD, with enoxaparin 4000 UI infused intravenously through the dialysis circuit 3 times per week for 3 years, and unfractionated heparin had been used to lock the catheter since the beginning. The platelet count was stable (between 200 and 240 000/mm3). On October 17, 6 months after the Polysulfone FX-80 dialyzer (Fresenius Medical Care) had been replaced with a polyacrylonitrile Evodial dialyzer (Hospal), the patient presented with dizziness and cyanosis at the beginning of HD. These symptoms recurred during the 2 following sessions (October 20 and 1
Pharmacovigilance Regional Centre of Burgundy, Dijon, France University Hospital, Dijon, France 3 University Hospital, Nancy, France 4 Hyphen Biomed, Neuville sur Oise, France 5 Hôpital Tenon, Paris, France 2
Corresponding Author: Aurélie Grandvuillemin, Pharmacovigilance Regional Center of Burgundy, 14 Rue P. Gaffarel, 21079 Dijon Cedex, France. Email: [email protected]
2
Annals of Pharmacotherapy
300
platelet (G/l)
250 200 HIT + 150 100
0
10/7 10/8 10/9 10/10 10/11 10/12 10/13 10/14 10/15 10/16 10/17 10/18 10/19 10/20 10/21 10/22 10/23 10/24 10/25 10/26 10/27 10/28 10/29 10/30 10/31 11/1 11/2 11/3 11/4 11/5 11/6 11/7
50
dialysis with enoxaparin
dialysis with danaparoid
Figure 1. Platelet count evolution.a a
Hemodialysis sessions.
Cyanosis, dizziness. Cardiac arrest.
22). An allergic reaction caused by ramipril and the polyacrylonitrile of the dialyzer membrane was suspected. Ramipril was stopped and the membrane was changed for a polysulfone Polyflux 210 H (Gambro). Then, on October 24, within 5 minutes of HD, the patient presented with dyspnea, cyanosis, and cardiac arrest. He quickly recovered with manual cardiopulmonary resuscitation and oxygen therapy. On the same day, the patient underwent a new session of HD using an FX 80 membrane and the usual anticoagulant enoxaparin. However, the patient showed cyanosis and loss of consciousness within 5 minutes. The symptoms quickly resolved with the administration of oxygen. HD was then continued with no further problems. The same events occurred during the 2 following HD sessions performed with Xenium 190 (October 27) and AM Bio HX 75 dialyzers (October 29). Considering these clinical events and the fall in the platelet count since October 24 (Figure 1), HIT was suspected. On October 29, the platelet count was measured before and after the HD session and showed a decrease from 132 to 82 G/L, suggesting HIT because the decrease seemed to be too great to be explained by platelet destruction by the dialyzer membrane. Leukocytes were in the normal range. Antivitamin K antagonist was withdrawn on October 29. Vitamin K was not administered because the INR was low (1.6) that day. There was no clotting in the dialyzer or in the extracorporeal circuit. Biological tests for HIT were performed on the same day. The platelet aggregation tests carried out according to Chong1 were positive
with heparin (and negative with saline). ELISA (enzymelinked immunosorbent assay) with the anti-PF4/heparin HPIA IgGAM kit (Stago, Asnières, France) was negative, and HemosIL anti-PF4/heparin was also negative (Instrumentation Laboratory, Bedford, MA). The total complement level was low (43%, 70 < N < 100), and IgE was within the normal range. HIT was confirmed by serotoninrelease assay.1 Doppler ultrasonography of the lower and upper limbs was performed but showed no signs of thrombosis. The venous catheter was removed because it had become dislodged. A Citra-Lock catheter instead of the unfractionated-heparin lock was used from October 29, as recommended by the American College of Chest Physicians Guidelines,2 and the following HD sessions (from October 31) were performed with danaparoid anticoagulation. No complications occurred. The patient received 3750 units of danaparoid during each HD session in accordance with the manufacturer’s recommendations. Oral anticoagulation with fluindione was restarted on October 31 because platelet count was increasing (149 G/L).2 The platelet count returned to the patient’s baseline level on November 3; 6 weeks later, ELISA remained negative, and platelet-aggregation tests were positive. The discordance between the functional assays (platelet-aggregation tests and serotoninrelease assay) and ELISA led us to search for a target other than PF4 for the antibodies. Surface plasmon resonance was performed as previously described,3 but no anti-IL8 antibodies (IgG and IgM) were detected, and the search for
3
Grandvuillemin et al antibodies against a mixture of PF4, IL8, and NAP2 with an HIT kit (Hyphen Biomed, Neuville sur Oise, France) was negative (IgG, IgM).
Discussion This case of HIT was unusual given the clinical context (low-molecular-weight heparin), the complications (cardiac arrest and no thrombosis), and timing (enoxaparin used for 3 years). According to the Naranjo probability scale, the causality of enoxaparin was evaluated as probable (ref 4). A 4T score (ref 5 and not 4) of 5 was found, even though this scale is not appropriate in the context of discontinuous exposure to heparin. Six cases of HIT and systemic symptoms during HD with unfractionated heparin have been published.(ref 6-11) Only Hartman et al (ref 12) reported 4 patients who developed acute HIT during HD with low-molecular-weight heparin (nadroparin), but the time to onset was short (within the first 5 HD sessions). In 3 of these patients, HD was performed in the postoperative period, and surgery is known to be a triggering factor for HIT. In most reported cases, clotting occurred in the extracorporeal system, and biological tests, including ELISA anti-PF4/heparin were often positive. The diagnosis of HIT in patients undergoing HD is difficult because the HD procedure itself is associated with a relative decrease in the platelet count and clotting in the extracorporeal circuit, despite apparently sufficient anticoagulation and vascular access. In our patient, the diagnosis of HIT was made in the presence of a drop in the platelet count from 132 G/L before HD to 82 G/L just after (>30%) and normalization of the platelet count under HD with danaparoid anticoagulation. HIT is well known for its thrombotic complications but less well known for acute systemic reactions. These clinical features have been clearly described by Warkentin (ref 13): the onset of typical signs and symptoms (dyspnea, cyanosis, dizziness, and collapse) 5 to 30 minutes after the heparin bolus. As in other reports, the IgE level was normal in our patient, which could exclude IgE-mediated anaphylaxis. We found no triggering factor for this case of HIT. The patient did not present with infection or inflammation and had not undergone surgery during the previous weeks. He had no recent history of treatment with unfractionated heparin or low-molecular-weight heparin apart from treatments given during HD sessions. The dialyzer membrane was suspected, but symptoms persisted when other membranes were used. Unfractionated-heparin had been used to lock the catheter since the beginning, as was usual in this nephrology unit. However, we cannot rule out the possibility that unfractionated-heparin, which is removed when using the catheter, may have diffused into the bloodstream from the catheter inadvertently and could have been a triggering factor. However medical staff in nephrology units is
well trained to use dialysis catheter (aspiration of anticoagulant used to lock the catheter before using it and administration of the required volume to lock the catheter after use). In our patient, systemic symptoms occurred on seven consecutive HD sessions, what allows us to exclude the role unfractionated-heparin through a misuse of the catheter. Biological tests are needed to confirm the diagnosis of HIT, and the association of a functional test (plateletaggregation test, serotonin-release assay) and an immunological test (ELISA) is recommended. In this case, plateletaggregation tests and the serotonin-release assay were clearly positive in the presence of heparin, but the ELISA to detect anti-PF4/heparin antibodies was negative. A target other than PF4 was searched for, such as anti-IL8 by surface plasmon resonance and antibodies against a mixture of PF4, IL8, and NAP2, but none of these were found to be the target. We can speculate that there may be a new target or a higher degree of sulfation related to components of the dialyzer membrane, but little information is available about the composition of these membranes. In conclusion, our patient experienced atypical HIT with systemic symptoms. The triggering factor was not found, but the patient’s symptoms and thrombocytopenia did not recur when danaparoid anticoagulation was used rather than enoxaparin. This sequence of events suggests that enoxaparin was responsible for the clinical symptoms and biological findings. HIT must be considered when acute systemic reactions occur at the beginning of an HD session, even after several years of HD and with no change in the anticoagulant used, including low-molecular-weight heparin. The platelet count should be measured immediately after the reaction. The diagnosis is important because of possible cardiac arrest in this context. Acknowledgments The authors acknowledge the assistance of the following people: M. Jean Pierre MAX for SPR analysis; Pr Bernard Tardy, Score TIH study coordinator because this patient was enrolled in the ongoing French multicenter study titled “Thrombopénie Induite par l’Héparine: Etablissement et Validation d’un Score Clinique de Prédiction”; and Philip Bastable for English reviewing.
Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.
References 1. Chong BH. Heparin-induced thrombocytopenia. J Thromb Haemost. 2003;1:1471-1478.
4 2. Linkins LA, Dans AL, Moores LK, et al. Treatment and prevention of heparin-induced thrombocytopenia: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141:e495S-e530S. 3. Regnault V, de Maistre E, Carteaux JP, et al. Platelet activation induced by human antibodies to interleukin-8. Blood. 2003;101:1419-1421. 4. Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981 :30(2):239-45. 5. Lo GK, Juhl D, Warkentin TE, Sigouin CS, Eichler P, Greinacher A. Evaluation of pretest clinical score (4 T’s) for the diagnosis of heparin-induced thrombocytopenia in two clinical settings. J Thromb Haemost. 2006;4:759-765. 6. Tholl U, Greinacher A, Overdick K, Anlauf M. Life-threatening anaphylactic reaction following parathyroidectomy in a dialysis patient with heparin-induced thrombocytopenia. Nephrol Dial Transplant. 1997;12:2750-2755. 7. Davenport A. Sudden collapse during haemodialysis due to immune-mediated heparin-induced thrombocytopaenia. Nephrol Dial Transplant. 2006;21:1721-1724.
Annals of Pharmacotherapy 8. Davenport A. Antibodies to heparin-platelet factor 4 complex: pathogenesis, epidemiology, and management of heparin-induced thrombocytopenia in hemodialysis. Am J Kidney Dis. 2009;54:361-374. 9. Tejedor A, Lopez Revuelta K, Garcia Bueno MJ, et al. Thrombocytopenia and anaphylaxis secondary to heparin in a hemodialysis patient. Clin Nephrol. 2005;63:226-240. 10. Kapa S, Qian Q. 84-Year old woman with hemodialysis-associated shortness of breath. Mayo Clin Proc. 2009;84:187190. 11. Popov D, Zarrabi M, Foda H, Graber M. Pseudopulmonary embolism: acute respiratory distress in the syndrome of heparin-induced thrombocytopenia. Am J Kidney Dis. 1997;29:449-452. 12. Hartman V, Malberain M, Daelemans R, Meersman P, Zachée P. Pseudo-pulmonary embolism as a sign of acute heparininduced thrombocytopenia in hemodialysis patients: safety of resuming heparin after disappearance of HIT antibodies. Nephron Clin Pract. 2006;104:c143-c148. 13. Warkentin TE. Heparin-induced thrombocytopenia and the anaesthesiologist. Can J Anaesth. 2002;49(suppl):S36S49.
research-article2014
AOPXXX10.1177/1060028014535361Annals of PharmacotherapyGrandvuillemin et al
Article
Unusual Case of HIT With Cardiac Arrest During Hemodialysis
Annals of Pharmacotherapy 1–4 © The Author(s) 2014 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1060028014535361 aop.sagepub.com
Aurélie Grandvuillemin, PharmD1, Gilbert Zanetta, MD2, Julien Perrin, MD3, Jean Amiral, MD4, Ismail Elalamy, MD5, and Emmanuel de Maistre, MD2
Abstract Objective: To report an unusual case of heparin-induced thrombocytopenia (HIT) with cardiac arrest during hemodialysis (HD). Case Summary: An 88-year-old man previously treated with HD under enoxaparin for 3 years presented with dizziness and cyanosis at the beginning of HD on 3 consecutive sessions. Even though the dialyzer membrane was changed, he presented with cardiac arrest, from which he recovered quickly. At the same time, the platelet count fell, and HIT was suspected. No thrombosis was found. Anti-PF4/H, IL8, and NAP2 antibodies were negative, but platelet aggregation tests and serotonin-release assay were positive. After implementing HD with danaparoid, the platelet count returned to normal, and the patient remained asymptomatic. Discussion: Given the clinical context (low-molecular-weight heparin), complications (cardiac arrest and no thrombosis), and timing (3 years), this was an unusual case of HIT. According to the Naranjo probability scale, the causality of enoxaparin was evaluated as probable. In most reported cases, time to onset was short, clotting occurred in the extracorporeal system, and biological tests, including ELISA (enzyme-linked immunosorbent assay) anti-PF4/heparin, were positive. We found no triggering factor in this case, and given the biological results, a new antigenic target may be involved. Conclusions: HIT must be considered when acute systemic reactions occur at the beginning of HD sessions, even after several years of HD and with no change of anticoagulant, including low-molecularweight heparin. The platelet count should be measured immediately after the reaction. The diagnosis is important because of possible cardiac arrest in this context. Keywords hemodialysis, heparin-induced thrombocytopenia, allergy
Introduction Heparin is the most commonly used extracorporeal anticoagulant for hemodialysis (HD), and heparin-induced thrombocytopenia (HIT) has been reported in this clinical context. This kind of adverse reaction may lead to thrombotic complications. In exceptional cases, acute systemic reactions can occur. According to published cases, the time to onset of these adverse reactions is usually short. We present a case of HIT that is unusual because of the clinical context, the complications, and timing.
Case Report An 88-year-old man had been treated with HD for 3 years. His main medical history included myocardial infarction, atrial fibrillation, and renal insufficiency. He had been treated with furosemide, vitamin K antagonist fluindione (with stable international normalized ratio [INR] between 2 and 3), atorvastatin, alfacalcidiol, cinacalcet, and ramipril.
He had undergone HD, with enoxaparin 4000 UI infused intravenously through the dialysis circuit 3 times per week for 3 years, and unfractionated heparin had been used to lock the catheter since the beginning. The platelet count was stable (between 200 and 240 000/mm3). On October 17, 6 months after the Polysulfone FX-80 dialyzer (Fresenius Medical Care) had been replaced with a polyacrylonitrile Evodial dialyzer (Hospal), the patient presented with dizziness and cyanosis at the beginning of HD. These symptoms recurred during the 2 following sessions (October 20 and 1
Pharmacovigilance Regional Centre of Burgundy, Dijon, France University Hospital, Dijon, France 3 University Hospital, Nancy, France 4 Hyphen Biomed, Neuville sur Oise, France 5 Hôpital Tenon, Paris, France 2
Corresponding Author: Aurélie Grandvuillemin, Pharmacovigilance Regional Center of Burgundy, 14 Rue P. Gaffarel, 21079 Dijon Cedex, France. Email: [email protected]
2
Annals of Pharmacotherapy
300
platelet (G/l)
250 200 HIT + 150 100
0
10/7 10/8 10/9 10/10 10/11 10/12 10/13 10/14 10/15 10/16 10/17 10/18 10/19 10/20 10/21 10/22 10/23 10/24 10/25 10/26 10/27 10/28 10/29 10/30 10/31 11/1 11/2 11/3 11/4 11/5 11/6 11/7
50
dialysis with enoxaparin
dialysis with danaparoid
Figure 1. Platelet count evolution.a a
Hemodialysis sessions.
Cyanosis, dizziness. Cardiac arrest.
22). An allergic reaction caused by ramipril and the polyacrylonitrile of the dialyzer membrane was suspected. Ramipril was stopped and the membrane was changed for a polysulfone Polyflux 210 H (Gambro). Then, on October 24, within 5 minutes of HD, the patient presented with dyspnea, cyanosis, and cardiac arrest. He quickly recovered with manual cardiopulmonary resuscitation and oxygen therapy. On the same day, the patient underwent a new session of HD using an FX 80 membrane and the usual anticoagulant enoxaparin. However, the patient showed cyanosis and loss of consciousness within 5 minutes. The symptoms quickly resolved with the administration of oxygen. HD was then continued with no further problems. The same events occurred during the 2 following HD sessions performed with Xenium 190 (October 27) and AM Bio HX 75 dialyzers (October 29). Considering these clinical events and the fall in the platelet count since October 24 (Figure 1), HIT was suspected. On October 29, the platelet count was measured before and after the HD session and showed a decrease from 132 to 82 G/L, suggesting HIT because the decrease seemed to be too great to be explained by platelet destruction by the dialyzer membrane. Leukocytes were in the normal range. Antivitamin K antagonist was withdrawn on October 29. Vitamin K was not administered because the INR was low (1.6) that day. There was no clotting in the dialyzer or in the extracorporeal circuit. Biological tests for HIT were performed on the same day. The platelet aggregation tests carried out according to Chong1 were positive
with heparin (and negative with saline). ELISA (enzymelinked immunosorbent assay) with the anti-PF4/heparin HPIA IgGAM kit (Stago, Asnières, France) was negative, and HemosIL anti-PF4/heparin was also negative (Instrumentation Laboratory, Bedford, MA). The total complement level was low (43%, 70 < N < 100), and IgE was within the normal range. HIT was confirmed by serotoninrelease assay.1 Doppler ultrasonography of the lower and upper limbs was performed but showed no signs of thrombosis. The venous catheter was removed because it had become dislodged. A Citra-Lock catheter instead of the unfractionated-heparin lock was used from October 29, as recommended by the American College of Chest Physicians Guidelines,2 and the following HD sessions (from October 31) were performed with danaparoid anticoagulation. No complications occurred. The patient received 3750 units of danaparoid during each HD session in accordance with the manufacturer’s recommendations. Oral anticoagulation with fluindione was restarted on October 31 because platelet count was increasing (149 G/L).2 The platelet count returned to the patient’s baseline level on November 3; 6 weeks later, ELISA remained negative, and platelet-aggregation tests were positive. The discordance between the functional assays (platelet-aggregation tests and serotoninrelease assay) and ELISA led us to search for a target other than PF4 for the antibodies. Surface plasmon resonance was performed as previously described,3 but no anti-IL8 antibodies (IgG and IgM) were detected, and the search for
3
Grandvuillemin et al antibodies against a mixture of PF4, IL8, and NAP2 with an HIT kit (Hyphen Biomed, Neuville sur Oise, France) was negative (IgG, IgM).
Discussion This case of HIT was unusual given the clinical context (low-molecular-weight heparin), the complications (cardiac arrest and no thrombosis), and timing (enoxaparin used for 3 years). According to the Naranjo probability scale, the causality of enoxaparin was evaluated as probable (ref 4). A 4T score (ref 5 and not 4) of 5 was found, even though this scale is not appropriate in the context of discontinuous exposure to heparin. Six cases of HIT and systemic symptoms during HD with unfractionated heparin have been published.(ref 6-11) Only Hartman et al (ref 12) reported 4 patients who developed acute HIT during HD with low-molecular-weight heparin (nadroparin), but the time to onset was short (within the first 5 HD sessions). In 3 of these patients, HD was performed in the postoperative period, and surgery is known to be a triggering factor for HIT. In most reported cases, clotting occurred in the extracorporeal system, and biological tests, including ELISA anti-PF4/heparin were often positive. The diagnosis of HIT in patients undergoing HD is difficult because the HD procedure itself is associated with a relative decrease in the platelet count and clotting in the extracorporeal circuit, despite apparently sufficient anticoagulation and vascular access. In our patient, the diagnosis of HIT was made in the presence of a drop in the platelet count from 132 G/L before HD to 82 G/L just after (>30%) and normalization of the platelet count under HD with danaparoid anticoagulation. HIT is well known for its thrombotic complications but less well known for acute systemic reactions. These clinical features have been clearly described by Warkentin (ref 13): the onset of typical signs and symptoms (dyspnea, cyanosis, dizziness, and collapse) 5 to 30 minutes after the heparin bolus. As in other reports, the IgE level was normal in our patient, which could exclude IgE-mediated anaphylaxis. We found no triggering factor for this case of HIT. The patient did not present with infection or inflammation and had not undergone surgery during the previous weeks. He had no recent history of treatment with unfractionated heparin or low-molecular-weight heparin apart from treatments given during HD sessions. The dialyzer membrane was suspected, but symptoms persisted when other membranes were used. Unfractionated-heparin had been used to lock the catheter since the beginning, as was usual in this nephrology unit. However, we cannot rule out the possibility that unfractionated-heparin, which is removed when using the catheter, may have diffused into the bloodstream from the catheter inadvertently and could have been a triggering factor. However medical staff in nephrology units is
well trained to use dialysis catheter (aspiration of anticoagulant used to lock the catheter before using it and administration of the required volume to lock the catheter after use). In our patient, systemic symptoms occurred on seven consecutive HD sessions, what allows us to exclude the role unfractionated-heparin through a misuse of the catheter. Biological tests are needed to confirm the diagnosis of HIT, and the association of a functional test (plateletaggregation test, serotonin-release assay) and an immunological test (ELISA) is recommended. In this case, plateletaggregation tests and the serotonin-release assay were clearly positive in the presence of heparin, but the ELISA to detect anti-PF4/heparin antibodies was negative. A target other than PF4 was searched for, such as anti-IL8 by surface plasmon resonance and antibodies against a mixture of PF4, IL8, and NAP2, but none of these were found to be the target. We can speculate that there may be a new target or a higher degree of sulfation related to components of the dialyzer membrane, but little information is available about the composition of these membranes. In conclusion, our patient experienced atypical HIT with systemic symptoms. The triggering factor was not found, but the patient’s symptoms and thrombocytopenia did not recur when danaparoid anticoagulation was used rather than enoxaparin. This sequence of events suggests that enoxaparin was responsible for the clinical symptoms and biological findings. HIT must be considered when acute systemic reactions occur at the beginning of an HD session, even after several years of HD and with no change in the anticoagulant used, including low-molecular-weight heparin. The platelet count should be measured immediately after the reaction. The diagnosis is important because of possible cardiac arrest in this context. Acknowledgments The authors acknowledge the assistance of the following people: M. Jean Pierre MAX for SPR analysis; Pr Bernard Tardy, Score TIH study coordinator because this patient was enrolled in the ongoing French multicenter study titled “Thrombopénie Induite par l’Héparine: Etablissement et Validation d’un Score Clinique de Prédiction”; and Philip Bastable for English reviewing.
Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.
References 1. Chong BH. Heparin-induced thrombocytopenia. J Thromb Haemost. 2003;1:1471-1478.
4 2. Linkins LA, Dans AL, Moores LK, et al. Treatment and prevention of heparin-induced thrombocytopenia: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141:e495S-e530S. 3. Regnault V, de Maistre E, Carteaux JP, et al. Platelet activation induced by human antibodies to interleukin-8. Blood. 2003;101:1419-1421. 4. Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981 :30(2):239-45. 5. Lo GK, Juhl D, Warkentin TE, Sigouin CS, Eichler P, Greinacher A. Evaluation of pretest clinical score (4 T’s) for the diagnosis of heparin-induced thrombocytopenia in two clinical settings. J Thromb Haemost. 2006;4:759-765. 6. Tholl U, Greinacher A, Overdick K, Anlauf M. Life-threatening anaphylactic reaction following parathyroidectomy in a dialysis patient with heparin-induced thrombocytopenia. Nephrol Dial Transplant. 1997;12:2750-2755. 7. Davenport A. Sudden collapse during haemodialysis due to immune-mediated heparin-induced thrombocytopaenia. Nephrol Dial Transplant. 2006;21:1721-1724.
Annals of Pharmacotherapy 8. Davenport A. Antibodies to heparin-platelet factor 4 complex: pathogenesis, epidemiology, and management of heparin-induced thrombocytopenia in hemodialysis. Am J Kidney Dis. 2009;54:361-374. 9. Tejedor A, Lopez Revuelta K, Garcia Bueno MJ, et al. Thrombocytopenia and anaphylaxis secondary to heparin in a hemodialysis patient. Clin Nephrol. 2005;63:226-240. 10. Kapa S, Qian Q. 84-Year old woman with hemodialysis-associated shortness of breath. Mayo Clin Proc. 2009;84:187190. 11. Popov D, Zarrabi M, Foda H, Graber M. Pseudopulmonary embolism: acute respiratory distress in the syndrome of heparin-induced thrombocytopenia. Am J Kidney Dis. 1997;29:449-452. 12. Hartman V, Malberain M, Daelemans R, Meersman P, Zachée P. Pseudo-pulmonary embolism as a sign of acute heparininduced thrombocytopenia in hemodialysis patients: safety of resuming heparin after disappearance of HIT antibodies. Nephron Clin Pract. 2006;104:c143-c148. 13. Warkentin TE. Heparin-induced thrombocytopenia and the anaesthesiologist. Can J Anaesth. 2002;49(suppl):S36S49.
