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Saudi Journal of Kidney Diseases and Transplantation
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CASE REPORT  
Year : 2021  |  Volume : 32  |  Issue : 6  |  Page : 1775-1781
Thrombocytopenia in a Hemodialysis Patient Starting Home Therapy with NxStage System One: Management in a Community Setting


Clinical Sciences Division, Northern Ontario School of Medicine, Sudbury and Thunder Bay, Ontario, Canada

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Date of Web Publication27-Jul-2022
 

   Abstract 


Platelet dysfunction is common in individuals with advanced chronic kidney disease, and hemodialysis (HD) may cause further activation of platelets, increasing the risk of bleeding and thrombosis. Thrombocytopenia is a potential complication of HD therapy that offen is multifactorial. Both underlying patient-related or specific HD factors may be responsible. We present a case where the patient developed new-onset thrombocytopenia while undergoing training for home HD using NxStage System One. We present a systematic approach in the evaluation and management of this patient that led us to continue with the completion of home HD training and later discharging him on home therapy.

How to cite this article:
Parmar MS. Thrombocytopenia in a Hemodialysis Patient Starting Home Therapy with NxStage System One: Management in a Community Setting. Saudi J Kidney Dis Transpl 2021;32:1775-81

How to cite this URL:
Parmar MS. Thrombocytopenia in a Hemodialysis Patient Starting Home Therapy with NxStage System One: Management in a Community Setting. Saudi J Kidney Dis Transpl [serial online] 2021 [cited 2022 Aug 15];32:1775-81. Available from: https://www.sjkdt.org/text.asp?2021/32/6/1775/352440



   Introduction Top


Platelet dysfunction (thrombasthenia) is common in individuals with advanced chronic kidney disease (CKD), and hemodialysis (HD) may cause further activation of platelets, increasing the risk of bleeding and throm-bosis.[1],[2] Thrombocytopenia, defined as low platelet count of less than 150,000 platelets/ mm3), is a potential complication of HD therapy and may result from several factors. We recently started a home HD program in a community setting and while training our second patient, we encountered new-onset thrombo-cytopenia after switching to home HD therapy in this patient. Here, we review the underlying causes, mechanisms responsible for thrombocytopenia and provide a systematic approach to its management and salvage of home HD modality.


   Case Report Top


A 56-year-old male with a history of hypertension, type 2 diabetes mellitus, ischemic heart disease, and diabetic kidney disease progressed rapidly over six-months to Stage 5 and needed to start HD while he was still waiting for arteriovenous access placement. He was started on conventional HD using a tunneled catheter three times per week. After further discussing options, he elected to consider home HD therapy because of the distance involved for in-center conventional therapy. After four months of conventional HD, he started undergoing home HD training using NxStage System One, and heparin as an anticoagulant was continued. After three to four weeks of training, blood work showed a significant drop in platelet count (from 172 to 107) that dropped to 83 [Figure 1], four days later.
Figure 1. Change in platelet count before after initiation of conventional hemodialysis and change to home hemodialysis therapy.

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What is prevalence of thrombocytopenia in patients undergoing hemodialysis?

In general, compared to healthy controls platelet counts in patients with advanced CKD (with or without dialysis) are slightly reduced because of reduced thrombopoiesis.[3],[4] In addition, during HD procedure, the platelet count typically falls by 5%−15% within the first 30 min of dialysis that invariably returns to baseline or slightly overshoots by the end of dialysis session[2],[5] and is thought to be because of complement activation either by various dialyzer membranes,[6],[7] sterilization methods,[8] or combination of both. However, thrombocytopenia was more frequent when using gamma-sterilized PUREMA® dialyzer − a part of the standard NxStage circuit and noted in 60% of children undergoing HD[9] and in over 50% of critically ill patients undergoing continuous renal replacement therapy.[10]

What are the causes of thrombocytopenia in patients receiving hemodialysis?

Individuals undergoing HD are at risk for thrombocytopenia from procedure-related factors, in addition to the underlying patient-related “general” factors [Table 1]. The procedure-related factors include the use of anticoagulants such as heparin to avoid clotting of the extracorporeal circulation, mechanical factors of blood passing through pumps, use of artificial membranes (dialyzers), and the sterilization techniques. The clinical manifestations may vary from asymptomatic, bleeding or thrombosis, depending on the pathophysiology and severity of thrombocytopenia.
Table 1. Mechanisms and causes of thrombocytopenia - in general population and specific to hemodialysis therapy.

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Heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is a complication of heparin therapy that could be nonimmune-mediated Type 1 resulting in platelet aggregation that manifests as mild, transient, benign thrombocytopenia,[11] or immune-mediated Type 2 caused by the development of antibodies to platelet factor 4 (PF4) and heparin that develops within five to 12 days of heparin exposure,[12] with incidence of 0.1%-5%. However, the risk of HIT among HD patients who experience repetitive heparin exposure, is no higher than the general population.[13] HIT develops in temporal association with heparin therapy and manifests either as an unexplained thrombocytopenia or thrombocytopenia complicated by thrombosis. The propensity for thrombosis distinguishes HIT from other drug-induced thrombocytopenias.[14] The 4Ts and HIT Expert Probability scoring systems[15] may be considered in the evaluation of individuals with suspected HIT. The diagnosis of HIT is often a combination of clinical and laboratory findings - elevated PF4 antibodies and positive platelet serotonin release assay. The presence of HIT antibodies is higher in HD patients and ranges up to 17.4%, however, the presence of HIT antibodies is not sufficient to make the diagnosis since antibody formation occurs in a variety of clinical settings without the development of thrombocytopenia or thrombosis.[16] When diagnosis is suspected, all sources of heparin should be discontinued and HD with no anticoagulation with frequent saline flushes, or regional citrate anticoagulation may be considered. Nonheparin anticoagulants (direct thrombin inhibitors, factor Xa inhibitors) may be considered to maintain the patency of extracorporeal circuit, but their use is limited by high cost and risk of anaphylactic reactions.

Dialyzer membrane-associated

thrombocytopenia

Vicks et al[17] reported severe thrombocytopenia in patient presenting with massive hemorrhage where thrombocytopenia resolved after changing the dialysis membrane and complement activation[5] with cuprophane membranes. Although advances in the development of biocompatible dialyzer membranes have reduced the incidence of thrombocytopenia, recent cases have been observed with polysulfone (PS) membranes,[18] and the platelet activation may differ substantially among PS membranes, depending on the manufacturer and the polyvinylpyrrolidone content.[2] Other reports linked the sterilization method of membranes to thrombocytopenia[19],[20] while others disputed this claim[21] and the exact cause still remains unknown[2] and is possibly a multifactorial and idiosyncratic complication.[22]

Approach to management of hemodialysis thrombocytopenia

Patients on HD may experience thrombocytopenia secondary to either underlying patient-related or HD-related factors or combination of both [Table 1], and a systematic approach is important in the management of thrombocytopenia in these individuals and is outlined in [Figure 2]. Dilutional and pseudothrombocytopenia should be considered early and excluded quickly with volume assessment and examination of peripheral smear for platelet clumping, and repeating platelet count using a different anticoagulant - citrate versus ethylenediaminetetraacetic acid.
Figure 2. Approach to new-onset thrombocytopenia in a hemodialysis patient.

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We wondered about other choices including converting the patient to conventional therapy, using an alternate anticoagulant or switching to peritoneal dialysis. However, all these options were possible but had some drawbacks, higher annual cost, and not supporting patient choice with conventional HD, and the higher cost if an alternate anticoagulant is used.[23] Converting the patient to peritoneal dialysis was an option, but the patient and family did not want to do that, so not in keeping with the patient choice. After reviewing the clinical history again, and the significant drop in platelet counts after he was switched to home HD, it was felt that thrombocytopenia is less likely to be HIT (as he has been heparin at least for four-months during his conventional intermittent HD) and a polyspecific ELISA HIT antibody test was negative. A Negative test has a 99% negative predictive value[24] we continued with home HD training and reduced heparin dose by 50% and used saline flushes if required while figuring out next steps. We reviewed the published literature and contacted experts in home HD at tertiary care centers for their opinions and recommendations. One of the experts (personal communication) had seen two cases and suggested asking the NxStage company to provide a different kit allowing us to use a different dialyzer after excluding HIT, and the other expert (personal communication) remarked it as a “tough” case and provided their own experience with a similar case[23] where they and others[25] had to switch patient to conventional HD and suggested alternate anticoagulation with the caveat that cost might be prohibitive. We felt that the thrombocytopenia was likely secondary to daily exposure to dialysis membrane but was unclear whether it was the membrane or the sterilization procedure and wondered if flushing the dialyzer with saline would help as Yang and Lindsay[26] reported the resolution of “dialyzer reaction” in a new HD patient by giving a predialyzer infusion of saline although understanding that was not a case of thrombocytopenia. Meanwhile, we came across, a “flush and dump” technique,[27] though not specific for the management of thrombocytopenia, where using 2 Ls of normal saline - the NxStage system is flushed with initial first liter of saline and then reprimed with the second liter, and we started using this “flush and dump” technique and continued with the home HD training of the patient and later successfully maintained him on home HD, resuming full dose of heparin, after a week of reduced dose with mild improvement of platelet counts that remain stable since.


   Conclusion Top


Thrombocytopenia in a HD patient is often complex and of multifactorial origin, and in addition to heparin-induced thrombocytopenia, it can be related to the biocompatibility and the sterilization methods of the dialyzers. A systematic approach is important in evaluating and managing these patients while considering safety and respecting patient choice, and avoiding unnecessary converting to conventional therapy from home HD.

Conflict of interest: None declared.

Disclosure:A short report of the case as Letter to Editor has since been published in Int Urol Nephrol 2021 PMID: 32940812.



 
   References Top

1.
Boccardo P, Remuzzi G, Galbusera M. Platelet dysfunction in renal failure. Semin Thromb Hemost 2004;30:579-89.  Back to cited text no. 1
    
2.
Daugirdas JT, Bernardo AA. Hemodialysis effect on platelet count and function and hemodialysis-associated thrombocytopenia. Kidney Int 2012;82:147-57.  Back to cited text no. 2
    
3.
Gafter U, Bessler H, Malachi T, Zevin D, Djaldetti M, Levi J. Platelet count and thrombopoietic activity in patients with chronic renal failure. Nephron 1987;45:207- 10.  Back to cited text no. 3
    
4.
Ando M, Iwamoto Y, Suda A, Tsuchiya K, Nihei H. New insights into the thrombopoietic status of patients on dialysis through the evaluation of megakaryocytopoiesis in bone marrow and of endogenous thrombopoietin levels. Blood 2001;97:915-21.  Back to cited text no. 4
    
5.
Hakim RM, Schafer AI. Hemodialysis-associated platelet activation and thrombocytopenia. Am J Med 1985;78:575-80.  Back to cited text no. 5
    
6.
Verbeelen D, Jochmans K, Herman AG, Van der Niepen P, Sennesael J, De Waele M. Evaluation of platelets and hemostasis during hemodialysis with six different membranes. Nephron 199;59:567-72.  Back to cited text no. 6
    
7.
Hoenich NA, Woffindin C, Brennan A, Cox PJ, Matthews JN, Goldfinch M. A comparison of three brands of polysulfone membranes. J Am Soc Nephrol 1996;7:871-6.  Back to cited text no. 7
    
8.
Docci D, Delvecchio C, Turci F, Baldrati L, Gollini C. Effect of different dialyzer membranes on serum angiotensin-converting enzyme during hemodialysis. Int J Artif Organs 1988;11:28-32.  Back to cited text no. 8
    
9.
Stronach L, Jones H, Hothi D. Dialyzer-induced thrombocytopenia in children using NxStage System (Abstract). Hemodial Int 2012;16:160.  Back to cited text no. 9
    
10.
Ferreira JA, Johnson DW. The incidence of thrombocytopenia associated with continuous renal replacement therapy in critically ill patients. Ren Fail 2015;37:1232-6.  Back to cited text no. 10
    
11.
Chang JJ, Parikh CR. When heparin causes thrombosis: Significance, recognition, and management of heparin-induced thrombocytopenia in dialysis patients. Semin Dial 2006;19:297-304.  Back to cited text no. 11
    
12.
Davenport A. Antibodies to heparin-platelet factor 4 complex: Pathogenesis, epidemiology, and management of heparin-induced thrombocytopenia in hemodialysis. Am J Kidney Dis 2009;54:361-74.  Back to cited text no. 12
    
13.
Pena de la Vega L, Miller R S, Benda MM, et al. Association of heparin-dependent antibodies and adverse outcomes in hemodialysis patients: A population-based study. Mayo Clin Proc 2005;80:995-1000.  Back to cited text no. 13
    
14.
Arepally GM, Ortel TL. Heparin-induced thrombocytopenia. Annu Rev Med 2010;61: 77-90.  Back to cited text no. 14
    
15.
Cuker A, Arepally GM, Chong BH, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: Heparin-induced thrombocytopenia. Blood Adv 2018;2:3360-92.  Back to cited text no. 15
    
16.
Hassell K. Heparin-induced thrombocytopenia: Diagnosis and management. Thromb Res 2008;123 Suppl 1:S16-21.  Back to cited text no. 16
    
17.
Vicks SL, Gross ML, Schmitt GW. Massive hemorrhage due to hemodialysis-associated thrombocytopenia. Am J Nephrol 1983;3:30-3.  Back to cited text no. 17
    
18.
Kobari E, Terawaki H, Takahashi Y, et al. Dialyzer-related thrombocytopenia due to a polysulfone membrane. Intern Med 2016;55: 965-8.  Back to cited text no. 18
    
19.
Bieber S, Ahmad S. Electron-beam sterilized hemodialyzers and thrombocytopenia. JAMA 2012;307:665.  Back to cited text no. 19
    
20.
Kiaii M, Djurdjev O, Farah M, Levin A, Jung B, MacRae J. Use of electron-beam sterilized hemodialysis membranes and risk of thrombocytopenia. JAMA 2011;306:1679-87.  Back to cited text no. 20
    
21.
Filiopoulos V, Manolios N, Vlassopoulos D. Use of electron-beam sterilized hemodialysis membranes is not associated with significant and persistent thrombocytopenia. Int J Artif Organs 2013;36:217-9.  Back to cited text no. 21
    
22.
Filiopoulos V, Vlassopoulos D. Hemodialysis-associated thrombocytopenia: A multifactorial and idiosyncratic complication. Am J Kidney Dis 2013;61:845.  Back to cited text no. 22
    
23.
Faratro R, D'Gama C, Chan C. The use of alternative anti-coagulation strategies for a nocturnal home hemodialysis patient with heparin-induced thrombocytopenia. CANNT J 2008;18:32-5.  Back to cited text no. 23
    
24.
Cuker A, Ortel TL. ASH evidence-based guidelines: Is the IgG-specific anti-PF4/heparin ELISA superior to the polyspecific ELISA in the laboratory diagnosis of HIT? Hematology Am Soc Hematol Educ Program 2009:250-2.  Back to cited text no. 24
    
25.
Sekkarie M, Waldron M, Reynolds T. NxStage dialysis system-associated thrombocytopenia: A report of two cases. Clin Nephrol 2016;85: 53-6.  Back to cited text no. 25
    
26.
Yang RC, Lindsay RM. Dialyzer reactions in a patient switching from peritoneal dialysis to hemodialysis. Hemodial Int 2005;9:120-6.  Back to cited text no. 26
    
27.
NxStage Second Flush Protocol. Vancouver: BC Renal Agency; 2017. Available from: http://www.bcrenalagency.ca/resource-gallery/ Documents/Second%20Flush%20Protocol.pdf. [Last accessed on 2019 Nov 05].  Back to cited text no. 27
    

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Correspondence Address:
Malvinder S. Parmar
Northern Ontario School of Medicine, Sudbury and Thunder Bay, Ontario, Canada.
Canada
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1319-2442.352440

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