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 Table of Contents  
CASE REPORT
Year : 2018  |  Volume : 3  |  Issue : 1  |  Page : 64-67

Postoperative atypical hemolytic uremic syndrome in nontransplant setting: A case report with review of literature


Department of Transfusion Medicine and Blood Bank, Artemis Hospitals, Gurgaon, Haryana, India

Date of Web Publication5-Apr-2018

Correspondence Address:
Dr. Urvershi Kotwal
Department of Transfusion Medicine and Blood Bank, Artemis Hospitals, Gurgaon, Haryana
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/GJTM.GJTM_61_17

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  Abstract 


Atypical hemolytic uremic syndrome (aHUS) is a clinical diagnosis characterized by a triad of microangiopathic hemolytic anemia, thrombocytopenia, and renal dysfunction. Postoperative aHUS in nontransplant patients is a rare entity. The proposed underlying mechanism is complement cascade dysregulation. aHUS has high morbidity and mortality. Prompt intervention with early initiation of therapeutic plasma exchange helps in the hematological remission thus reducing morbidity.

Keywords: Atypical hemolytic uremic syndrome, complement dysregulation, postoperative, therapeutic plasma exchange


How to cite this article:
Khetarpal A, Gupta V, Kotwal U. Postoperative atypical hemolytic uremic syndrome in nontransplant setting: A case report with review of literature. Glob J Transfus Med 2018;3:64-7

How to cite this URL:
Khetarpal A, Gupta V, Kotwal U. Postoperative atypical hemolytic uremic syndrome in nontransplant setting: A case report with review of literature. Glob J Transfus Med [serial online] 2018 [cited 2018 Aug 17];3:64-7. Available from: http://www.gjtmonline.com/text.asp?2018/3/1/64/229343




  Introduction Top


Hemolytic uremic syndrome (HUS) is characterized by triad of nonimmune hemolytic anemia, thrombocytopenia, and renal dysfunction.

Atypical HUS (aHUS) accounts for 5%–10% of HUS.[1] Postoperative aHUS is uncommon entity and is a diagnosis of exclusion which needs to be differentiated from other causes of postoperative anemia, thrombocytopenia, and renal failure. aHUS has poor prognosis, with mortality up to 25% and progression to ESRD in half of the patients.[2] High clinical suspicion is pivotal for early recognition to reduce mortalities. Prompt intervention and early initiation of therapeutic plasma exchange help in hematological remission reducing morbidity. We hereby report an unusual case of postoperative aHUS in a nontransplant setting.


  Case Report Top


A 39-year-old female with Grade-IV endometriosis, underwent laparoscopic hysterectomy. Intraoperatively, she developed severe hypotension for which the procedure was halted and later converted to conventional laparotomy. Postoperatively, the patient developed oliguria which was managed conservatively. Patient's rising creatinine levels suggested acute kidney injury. Dialysis was started on the second postoperative day (POD) (creatinine level ~4.54). This was followed by steady fall of hemoglobin and platelets and showed 4%–5% schistocytes on peripheral smear. The patient was afebrile with no neurological symptoms. DCT and ICT were negative. Lactate dehydrogenase (LDH) was raised ~3103.9 U/l. Summary of the pertinent laboratory investigations is given in [Table 1]. A clinical diagnosis of aHUS was made. The patient was not willing for renal biopsy and molecular testing.
Table 1: Summary of all laboratory investigations done during the hospital stay

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Pulse methylprednisolone was given for 3 days and tapered eventually, followed by nine daily sessions of therapeutic plasma exchange (TPE) starting on POD-6 with fresh frozen plasma (FFP) as replacement fluid were done on Com-Tec continuous cell separator. In each session, 1-1.2 plasma volume was exchanged.

Her hematological profile [Table 2] and [Figure 1] improved (↑platelet-count and ↓ LDH) after 2 procedures and was discharged on POD-16 on maintenance dialysis.
Table 2: Serial hematological and renal parameters during the hospital stay

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Figure 1: Figure showing serial changes in the LDH, Platelets, Hb & creatinine levels during the hospital stay

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  Discussion Top


Thrombotic microangiopathies (TMAs) though rare in postoperative period, usually present either as aHUS or thrombotic thrombocytopenic purpura (TTP). Although clinical overlap exists between aHUS and TTP, there are features which favor one over the other. While renal symptoms predominate in aHUs, TTP has predominant neurological manifestations. The clinical onset for TTP is around fifth to ninth postoperative day. while it is immediate in aHUS. TTP is associated with either antibodies to ADAMTS-13 or its reduced levels. The postulated etiopathogenesis of postoperative TTP is release of large amount of vWF multimers secondary to endothelial damage due to surgical manipulations which exhausts the available metalloproteinases. While for aHUS, it is postulated that surgical manipulations in susceptible individuals might trigger the dysregulation and amplification of alternate pathway complement proteins.[2],[3]

Dysfunction of the alternate complement pathway regulator proteins play an important role in the pathogenesis of aHUS [4] and discovery of complement factor H (CFH) mutations (20%–30%) emphasized the genetic role as etiology. Membrane cofactor protein mutations (10%–15%), mutations affecting CFI (4%–10%), C3 (5%–10%), complement factor B (1%–2%), and thrombomodulin (3%–5%) have also been reported.[1],[5] In about 6%–10% of patients with aHUS, anti-CFH autoantibodies have been found.[5]

Although above alterations predispose to the development of aHUS, it often requires a secondary trigger [1],[6] such as infections (Streptococcus pnuemoniae, N-meningitides, etc.), drugs, pregnancy (10%–20%), transplants, autoimmune disorders, and malignancies to manifest.[6]

Postoperative aHUS is commonly reported after organ transplantation as either a recurrence,[7]de novo or as a complication of drugs, viruses. Postoperative aHUS developing in adults in nontransplant surgical procedures is a rare phenomenon.[3]

Among the four cases of aHUS developing after nontransplantation surgeries as mentioned in literature, three of them were adults [2],[3],[8] and one was a pediatric case.[6] These patients developed signs and symptoms within a few days after surgery. High mortality associated with aHUS warrants immediate treatment even in the absence of confirmation of diagnosis.[2]

Confirmation takes a long time requiring detection of genetic abnormalities which may not be detected in up to half of the patients even after thorough investigations.[3] Likewise, out of the three cases mentioned, testing for genetic abnormalities in the complement regulation system was done and abnormality found only in two. The genetic study could not be done in our case like the other case reported.[2]

In our study, testing for the complement levels showed normal results not supplementing the diagnosis of aHUS. Quantitative complement proteins assays lack sensitivity and specificity and thus may not always be helpful.[9]

The initiation of TPE in our case achieved early hematological recovery without improving renal function. Unknown mechanisms are postulated for the progressive renal failure.[1],[7] The threshold for complement activation responsible for renal impairment is supposed to be lower. TPE is more effective for hematological response but not for the renal damage [3],[7]

TPE is recommended as the first-line treatment.[10] It is recommended that 1.5 plasma-volume (60–75 ml/kg) be exchanged per se ssion, replaced by FFP.[11] When TPE cannot be performed within 24 h of presentation, plasma infusions of 10–20 ml/kg should be given if there is no volume overload.[11]

Despite conflicting reports of the effectiveness, TPE is preferred over plasma infusion due to potential therapeutic benefits without risk of volume overload, hyperproteinemia, or refractoriness.[10]

Screening in some of the patients has shown a pathogenic complement gene mutation predisposing them to risk of recurrence warranting long-term therapy to maintain remission, though a few completely responded to TPE.[7]

It is recommended that even after 3–5 TPE on a daily basis the persistence of hemolysis or lack of improvement in renal function should be regarded as an indication to maintain daily TPE or to switch the patient to eculizumab.[11]

Therefore, postoperative aHUS in nontransplant settings which earlier was thought to be uncommon should be suspected in all the postoperative patients who develop TMA soon after surgery.[3]

Although TPE is not the definitive management for such cases, early initiation is important achieving hematological remission.

aHUS has a known risk of recurrence;[5],[7] therefore, for patients who are resistant/partially responsive or have recurrences, eculizumab is the drug of choice. Eculizumab is a complement inhibitor with hematological and renal response in over 80% of patients.[11] This was not available for our patient.

Thus, high degree of clinical suspicion for early diagnosis along with the immediate initiation of TPE in combination with eculizumab should be the mainstay of treatment which may prevent the occurrence of irreversible end-stage renal failure in aHUS in nontransplant surgical cases.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Noris M, Remuzzi G. Hemolytic Uremic syndrome. J Am Soc Nephrol 2005;16:1035-50.  Back to cited text no. 1
    
2.
Lee JW, Won NH, Cho E, Kim MG, Jo SK, Cho WY, et al. Postoperative Hemolytic Uremic syndrome with renal cortical necrosis following laparoscopic hemicolectomy. Ren Fail 2013;35:725-8.  Back to cited text no. 2
    
3.
Yasuda S, Yamamoto M, Fukuda T, Ohtsuka Y, Miura O. Postoperative atypical Hemolytic Uremic syndrome treated successfully with eculizumab. Intern Med 2016;55:1171-5.  Back to cited text no. 3
    
4.
Noris M, Caprioli J, Bresin E, Mossali C, Pianetti G, Gamba S, et al. Relative role of genetic complement abnormalities in sporadic and familial aHUS and their impact on clinical phenotype. Clin J Am Soc Nephrol 2010;5:1844-59.  Back to cited text no. 4
    
5.
Noris M, Remuzzi G. Review article: Atypical hemolytic – Uremic syndrome. N Engl J Med 2009;361:1676-87.  Back to cited text no. 5
    
6.
Matsukuma E, Imamura A, Iwata Y, Takeuchi T, Yoshida Y, Fujimura Y, et al. Postoperative atypical hemolytic uremic syndrome associated with complement c3 mutation. Case Rep Nephrol 2014;2014:784943.  Back to cited text no. 6
    
7.
Scully M, Goodship T. How I treat thrombotic thrombocytopenic purpura and atypical haemolytic uraemic syndrome. Br J Haematol 2014;164:759-66.  Back to cited text no. 7
    
8.
Matsumoto T, Fan X, Ishikawa E, Ito M, Amano K, Toyoda H, et al. Analysis of patients with atypical hemolytic uremic syndrome treated at the Mie University Hospital: Concentration of C3 p.I1157T mutation. Int J Hematol 2014;100:437-42.  Back to cited text no. 8
    
9.
Afshar-Kharghan V. Complementing the diagnosis of aHUS. Blood 2014;124:1699-700.  Back to cited text no. 9
    
10.
Schwartz J, Winters JL, Padmanabhan A, Balogun RA, Delaney M, Linenberger ML, et al. Guidelines on the use of therapeutic apheresis in clinical practice-evidence-based approach from the writing committee of the American Society for Apheresis: The sixth special issue. J Clin Apher 2013;28:145-284.  Back to cited text no. 10
    
11.
Loirat C, Frémeaux-Bacchi V. Atypical hemolytic uremic syndrome. Orphanet J Rare Dis 2011;6:60.  Back to cited text no. 11
    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2]



 

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