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 Table of Contents  
CASE REPORT
Year : 2022  |  Volume : 18  |  Issue : 4  |  Page : 233-236

Sepsis-induced autoimmune hemolytic anemia in the elderly


1 Department of Geriatric Medicine, Madras Medical College, Chennai, Tamil Nadu, India
2 Department of Geriatric Medicine, Government Mohan Kumaramangalam Medical College, Salem, Tamil Nadu, India
3 Department of Geriatric Medicine, Affinity Elder Care, Coimbatore, Tamil Nadu, India

Date of Submission09-Nov-2022
Date of Acceptance11-Dec-2022
Date of Web Publication27-Dec-2022

Correspondence Address:
D Thangam
Department of Geriatric Medicine, Madras Medical College, Chennai, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jiag.jiag_61_22

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  Abstract 


Autoimmune hemolytic anemia (AIHA) secondary to hematological malignancy is well-known and common in the elderly. AIHA associated with infection is less commonly reported in the elderly. We are reporting a case of AIHA in an elderly female with comorbidities, probably secondary to Gram-negative infection. The case was admitted and treated during the peak of the second wave of the COVID pandemic. The treatment of AIHA also had an impact on the progress and outcome of the underlying disease, leading to readmission in a short span of time. The patient also developed a thrombotic complication known to be associated with AIHA.

Keywords: Autoimmune hemolytic anemia, sepsis, AIHA, Gram negative infection,elderly


How to cite this article:
Thangam D, Deepa S, Kumar P D, Manikandan P S. Sepsis-induced autoimmune hemolytic anemia in the elderly. J Indian Acad Geriatr 2022;18:233-6

How to cite this URL:
Thangam D, Deepa S, Kumar P D, Manikandan P S. Sepsis-induced autoimmune hemolytic anemia in the elderly. J Indian Acad Geriatr [serial online] 2022 [cited 2023 Feb 8];18:233-6. Available from: http://www.jiag.com/text.asp?2022/18/4/233/365781




  Introduction Top


Autoimmune hemolytic anemia (AIHA) is the most common extracorpuscular hemolytic anemia.[1] They are related to the presence of autoantibodies directed against components of the erythrocyte membrane. They have a wide range of etiologies, can present suddenly, and progress to potentially serious problems.[2] Hence, they need rapid and well-codified management which includes treatment of the trigger.

There are few references in the literature regarding AIHA in the elderly. The risk of AIHA increases with age, the risk is 5 times higher in the 7th decade of life compared to the 4th decade.


  Case Report Top


A 60-year-old female patient got admitted on May 15, 2021, as an inpatient in the geriatric medicine ward, with a history of fever with rigors, burning micturition, fatigue, anorexia, nausea, vomiting, and dull aching right-sided abdominal pain predominantly in the right lumbar region, and loin of 4-day duration. She noticed reduced urine output for 2 days before admission along with pedal edema.

She was a known case of diabetes and thyroid disorder, and she discontinued the medications for both conditions a few weeks before the admission. She was evaluated the previous day outside with an ultrasound abdomen, which was reported as right-sided pyelonephritis.

On examination, the patient was looking sick, afebrile, tachypneic, and anemic. She was not jaundiced. She had bilateral pedal edema. Her vitals were stable. Abdominal examination revealed severe tenderness in right hypochondrial region, lumbar region, and right renal angle. The abdomen was soft, and there was no free fluid.

Initial blood investigations showed moderate anemia, thrombocytopenia, and direct hyperbilirubinemia with normal liver enzyme levels. There was evidence of acute kidney injury, hyponatremia, and mild hyperkalemia. She had very high blood sugar and metabolic acidosis, and her urine was positive for ketones. COVID screening was negative. Urine deposits showed 4–6 pus cells. This is shown in [Table 1]. The plain computed tomography (CT) abdomen confirmed the diagnosis of acute pyelonephritis. It is shown in [Figure 1]. Initial diagnosis of uncontrolled diabetes mellitus, acute pyelonephritis with sepsis, and multiorgan dysfunction was made.
Table 1: Blood investigations

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Figure 1: CT abdomen (plain) – right Kidney appears enlarged with perinephric fat strandings associated with anterior and posterior pararenal fascia. CT: Computed tomography

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She was started on meropenem and other supportive measures to take care of metabolic derangement. Nephrologist and urologist have been periodically reviewing her. After initial treatment, she developed fever spikes for up to 7 days. Urine culture growing Klebsiella 103 and Candida nonalbicans. With the introduction of antifungals, her fever settled. This is shown in [Table 2].
Table 2: Other investigations

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With treatment, there was an overall improvement in laboratory parameters. However, complete blood count showed worsening anemia and the patient developed grade 2 exertional dyspnea, increasing pedal edema, and fatigue. A packed red blood cell (PRBC) transfusion was planned, but the cross-matching sample did not match with any of the blood groups. AIHA was considered, and direct Coomb's test was done, and it was positive. This is shown in [Table 3]. Hematologist's advice was sought. 2 units of the most compatible PRBC transfusion was done on 2 separate days under the cover of methylprednisolone 1 g. Methylprednisolone was continued for another 3 days, followed by oral steroids.
Table 3: Investigations for anemia

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Further investigations for finding the cause of AIHA were carried out. It is shown in [Table 3]. viral markers were negative. There was no lymph node enlargement (physical examination and CT of abdomen and chest), Rheumatological investigations were negative for any autoimmune disorders (antinuclear antibody, double-stranded DNA, C-reactive protein, Hep2 neg, and normal C3, C4). Screening for multiple myeloma was negative. Marrow examination was normal. Fine-needle aspiration cytology thyroid was done as the patient had multinodular goiter (thyroid normalcy), which was also negative for malignancy. This is shown in [Table 4].
Table 4: Investigations to find out the cause of hemolytic anemia

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Since there was no other reason which could explain AIHA, the diagnosis of Gram-negative sepsis-induced AIHA was made. Since the contrast-enhanced CT abdomen showed evidence of pyelonephritis with multiple subcortical abscesses, in consultation with a nephrologist and urologist, the patient was started on oral fosfomycin and fluconazole. Both were continued for a total of 6 weeks. The patient was followed up as an outpatient. The repeat urine culture was negative for bacterial and fungal elements. According to the hematologist's advice, steroids were tapered and stopped. The patient reported normal health.

Six weeks later, she again presented with severe left-sided abdominal pain, fever, and recurrent vomiting of 4-day duration. She was febrile and in shock. Ultrasound imaging showed left pyelonephritis, resolving right pyelonephritis. As per the urologist advice, DJ stenting was done. The urine culture grew Klebsiella 105. After being shifted to the geriatric ward from urology, she complained of severe left leg pain, and Doppler studies confirmed left popliteal vein thrombosis. This is shown in [Table 5] and [Table 6]. Hematology review was sought and have advised to restart low-dose steroids and also anticoagulation. The patient is discharged on these along with OHA and antihypertensives.
Table 5: Investigations on readmission

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Table 6: Other investigations on readmission

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  Discussion Top


AIHA is the most common extracorpuscular hemolytic anemia.[1] It can present as a serious acute illness with a wide range of etiologies.[2] Hence, they need rapid and well-codified management which includes treatment of the trigger.

There are few references in the literature regarding AIHA in the elderly. The risk of AIHA increases with age, the risk is 5 times higher in the 7th decade of life compared to the 4th decade. This could be mainly due to age-related immunosenescence. Genetic background, immunodeficiency, autoimmune disease, infections, medications, neoplasias particularly Chronic lymphoid leukemia, Non Hodgkin's Lymphoma, and transplants have all been suggested as risk factors for AIHA. About half of cases of warm AIHA are recognized as secondary to underlying diseases among others, infections. Development of molecular mimicry between self-antigens and pathogen antigens has been highlighted as one of the pathogenic mechanisms responsible for the induction and progression of hemolysis.[3]

Similarly, several mechanisms are proposed for the increased occurrence of venous thromboembolism in AIHA.

Some of them are as follows:

Autoimmune destruction of RBC membrane leads to increased exposure of the membrane phosphatidyl serine and release of microparticles. This promotes the enzymatic complexes of coagulation which in turn enhances the conversion of factor X to Xa and thus prothrombin to thrombin.[4] Destruction of RBCs releases ADP which induces platelet aggregation.[5] Cell-free hemoglobin enhances the expression of ICAM-1, an intracellular adhesion molecule along with the pro-inflammatory effect of free heme can alter endothelial regulation and can activate coagulation.[6],[7],[8] Besides the mechanisms described above, the treatment itself (in particular glucocorticoids) may contribute to the prothrombotic state in patients with AIHA.[9]

In our case, the patient manifested hemolysis due to infection. It came to light during the first admission when there was a rapid development of anemia, failure symptoms, and signs along with laboratory evidence of hemolysis. Immunologic basis for the hemolysis was evidenced by positive Coombs test, difficulty in cross-matching, and response to steroids. The other common hematological and infectious causes were ruled out. As per the literature, some of the secondary AIHA patients need prolonged steroid maintenance therapy.[2] Our patient also needed steroid cover for blood transfusion during the second admission and is being continued. She developed thrombotic complications in the form of popliteal vein thrombosis which needed anticoagulation.[3] In a case series, examining thrombotic complications associated with AIHA, secondary AIHA related to HCV, DVT is reported in a 54-year-old male.[10]

She grew the same organism (Klebsiella) two times. Similar case report wherein an elderly patient with cholecystitis and Gram-negative sepsis due to  Escherichia More Details coli developing AIHA is reported in the literature.[11] That is probably the only other such reported case in a case of Gram-negative bacterial sepsis. There are several reports of AIHA in the elderly secondary to hematologic malignancies, which is fairly a common occurrence.

In our case, the other points of concern are, the patient has to be on maintenance steroids which are likely to interfere healing of pyelonephritis/cause exacerbations. This is also already evidenced in our case by imaging which shows active left-sided kidney disease compared to the previous one. She is a diabetic and control of that can also be a problem. She is also susceptible to complications which can arise due to chronic anticoagulation.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Rochant H. Autoimmune hemolytic anemia. Rev Prat 2001;51:1534-41.  Back to cited text no. 1
    
2.
Valent P, Lechner K. Diagnosis and treatment of autoimmune haemolytic anaemias in adults: A clinical review. Wien Klin Wochenschr 2008;120:136-51.  Back to cited text no. 2
    
3.
Michalak SS, Olewicz-Gawlik A, Rupa-Matysek J, Wolny-Rokicka E, Nowakowska E, Gil L. Autoimmune hemolytic anemia: Current knowledge and perspectives. Immun Ageing 2020;17:38.  Back to cited text no. 3
    
4.
Cappellini MD. Coagulation in the Pathophysiology of Hemolytic Anemias. Hematology Am Soc Hematol Educ Program 2007;2007:74-8. doi: https://doi.org/10.1182/asheducation-2007.1.74.  Back to cited text no. 4
    
5.
Helms CC, Marvel M, Zhao W, Stahle M, Vest R, Kato GJ, et al. Mechanisms of hemolysis-associated platelet activation. J Thromb Haemost 2013;11:2148-54.  Back to cited text no. 5
    
6.
Rother RP, Bell L, Hillmen P, Gladwin MT. The clinical sequelae of intravascular hemolysis and extracellular plasma hemoglobin: A novel mechanism of human disease. JAMA 2005;293:1653-62.  Back to cited text no. 6
    
7.
Chen G, Zhang D, Fuchs TA, Manwani D, Wagner DD, Frenette PS. Heme-induced neutrophil extracellular traps contribute to the pathogenesis of sickle cell disease. Blood 2014;123:3818-27.  Back to cited text no. 7
    
8.
Weidmann H, Heikaus L, Long AT, Naudin C, Schlüter H, Renné T. The plasma contact system, a protease cascade at the nexus of inflammation, coagulation and immunity. Biochim Biophys Acta Mol Cell Res 2017;1864:2118-27.  Back to cited text no. 8
    
9.
Solari D, Alberio L, Ribi C, Grandoni F, Stalder G. Autoimmune hemolytic anemia and pulmonary embolism: An association to consider. TH Open 2021;5:e8-13.  Back to cited text no. 9
    
10.
Audia S, Bach B, Samson M, Lakomy D, Bour JB, Burlet B, et al. Venous thromboembolic events during warm autoimmune hemolytic anemia. PLoS One 2018;13:e0207218.  Back to cited text no. 10
    
11.
Lantinga MA, Polderman FN, Issa DE, de Jager CP. Jaundice due to autoimmune haemolytic anaemia in a patient with Gram-negative septic shock. Neth J Crit Care 2021;29:28-30.  Back to cited text no. 11
    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

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