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 Table of Contents  
Year : 2021  |  Volume : 1  |  Issue : 4  |  Page : 263-265

Acute intravascular hemolysis in the critical phase of severe dengue

Department of Pediatrics, Pediatric Intensive Care Unit, Faridabad, Haryana, India

Date of Submission11-Aug-2021
Date of Decision27-Oct-2021
Date of Acceptance07-Nov-2021
Date of Web Publication29-Nov-2021

Correspondence Address:
Dr. Sonali Ghosh
Department of Pediatrics, Pediatric Intensive Care Unit, QRG Health City, Sector 16 A, Faridabad - 121 002, Haryana
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ipcares.ipcares_254_21

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Background: Dengue and severe dengue have various hemorrhagic manifestations ranging from mild presentations such as petechiae, bleeding from injection sites, ecchymosis, and gum bleeding to severe presentations like major mucosal bleeding such as hematemesis, melena, menorrhagia, and concealed internal bleeding. Common causes of anemia in dengue are due to blood loss (secondary to thrombocytopenia and/or coagulopathy), transient suppression of the bone marrow, and rarely, hemolytic anemia. Clinical Description: We describe a 5-year-old boy who presented to us in the critical phase of severe dengue with features of capillary leakage and cola-colored urine. Salient investigation reports were anemia, thrombocytopenia, normal reticulocyte count, absence of coagulopathy, indirect hyperbilirubinemia, deranged transaminase, highly elevated lactate dehydrogenase, and low haptoglobin levels, and hemoglobinuria, suggestive of acute intravascular hemolysis (AIVH). Autoimmune and microangiopathic hemolytic anemia, malaria, ingestion of dyes, snake bite, Glucose 6 phosphate dehydrogenase deficiency, and incompatible blood transfusions were excluded. Thus, the final diagnosis was severe dengue with hemolytic anemia and AIVH. Management: Oxygen delivery by the Heated Humidified High-Flow Nasal Cannula, strict input/output charting, appropriate fluid therapy, and diuretic infusion were the mainstays of management in an intensive setting. The aim was to maintain ventilation, perfusion, balance hydration, achieve optimal urine output and prevent fluid overload. Conclusion: Clinicians should consider Dengue as a possible cause for AIVH in children with severe dengue and cola-colored urine.

Keywords: Acute Intravascular hemolysis, dengue fever, hemolytic anemia

How to cite this article:
Ghosh S, Mahajan L. Acute intravascular hemolysis in the critical phase of severe dengue. Indian Pediatr Case Rep 2021;1:263-5

How to cite this URL:
Ghosh S, Mahajan L. Acute intravascular hemolysis in the critical phase of severe dengue. Indian Pediatr Case Rep [serial online] 2021 [cited 2022 Jan 20];1:263-5. Available from: http://www.ipcares.org/text.asp?2021/1/4/263/331374

Dengue is a common viral infection caused by four serotypes of the Flaviviridae family (DENV 1, DENV 2, DENV 3, and DENV 4). Affected individuals may be asymptomatic or exhibit a diverse range of multi-systemic clinical manifestations and complications.[1] The World Health Organization classifies the illness as “Dengue (with or without warning signs)” and “Severe dengue.” The latter encompasses potentially lethal complications, due to plasma leakage, fluid accumulation, respiratory distress, severe bleeding, or organ impairment (hepatic, cardiac, or central nervous system). After an incubation period of 5–7 days, the course of illness comprises three sequential phases: A febrile phase (that may be biphasic and last for 2–7 days), a critical phase (starting with defervescence and lasting for 24–48 h), and a convalescent phase.

Hematological manifestations are common due to the existing thrombocytopenia and coagulopathy. These include petechiae, mucosal bleeds, hematoma formation, and severe bleeding manifestations such as hematemesis, melena, or intracranial bleeds.[2] Thus, anemia in dengue can result from blood loss or transient bone marrow suppression. There have been rare reports of adults presenting with hemolytic anemia,[3],[4],[5],[6],[7] but hardly in children/adolescents. After a literature search, we could identify a single description of acute intravascular hemolysis (AIVH) in a 17-year-old Sri Lankan boy in the febrile phase of dengue.[8]

We report a case of AIVH noted in the critical phase in a much younger boy. To the best of our knowledge, this has not been reported earlier from India.

  Clinical Description Top

A 5-year-old previously healthy, boy presented with high-grade fever for 6 days, associated with generalized malaise. On the 1st day of the fever, his parents had consulted a primary care physician who had prescribed some oral medication, the details of which were not available. On the 3rd day of fever, he developed loose watery stools and nonprojectile, nonbilious, vomiting. His oral intake became poor, though the frequency of urine output was unchanged, and color was normal. There was no difficulty in breathing, bleeding from any site, or rashes. The child was hospitalized and diagnosed and managed as severe dengue, based on a positive dengue Non-Structural Antigen 1 report with anemia, thrombocytopenia, and deranged liver function tests. He developed respiratory distress on the 6th day of fever, requiring oxygen support. He was referred to our center on day 6 for further management.

At presentation, the patient was afebrile, conscious, and alert. The heart rate was 54/min (sinus rhythm); respiratory rate 54/min with the use of accessory muscles of respiration; and noninvasive blood pressure recorded as 103/70 mm Hg (right arm supine position). Pallor and icterus were present. There were no skin rashes or lymphadenopathy. His weight was 15 kg (10th centile for age), height 109 cm (25th centile for age), and weight for height at 25th centile for age. Salient systemic examination findings were decreased air entry in both lung fields with no additional breath sounds, and soft hepatomegaly with a liver span of 8 cm. Dark cola-colored urine was observed on Foley's catheterization [Figure 1]. On retrospective history taking, we were unable to elicit recent travel, recurrent abdominal pain, ingestion of any substance, food, or medicine containing dyes known to change urinary color (other than those prescribed on the 1st day, though 6 days had elapsed). There was no history of any recent blood transfusion or surgery.
Figure 1: Urine samples of the patient on day 1 (left) and day 6 (right) of admission

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Investigations confirmed anemia, thrombocytopenia, hepatitis [Table 1], and a normal coagulation profile. A very high level of Lactate dehydrogenase (LDH), presence of 3–5 red blood cells/high power field (RBCs/HPF) on urine microscopy, and hemoglobin on urine spectrophotometry were indicative of hemolytic anemia secondary to AIVH. Further workup showed a normal reticulocyte count (1%), low serum haptoglobin levels (<30 mg/dl, normal range 40–280 mg/dl), and negative direct and indirect Coomb's test. Malaria was excluded by peripheral smear and rapid malaria antigen test. The qualitative test for Glucose 6 phosphate dehydrogenase (G6PD) was normal. No abnormal cells or evidence of agglutination was seen in the peripheral blood smear. The trend of salient hematological reports after admission is given in [Table 1]. The chest X-ray showed bilateral pleural effusion, whereas an abdominal ultrasound detected free fluid in the abdominal cavity. Serological tests for Hepatitis A and Hepatitis E were negative.
Table 1: Laboratory parameters during the febrile and critical phase of dengue in the patient

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Management and outcome

The child was managed in the Pediatric Intensive Care Unit (for severe respiratory distress due to fluid overload. He was started on oxygen delivery by Heated Humidified High Flow Nasal Cannula (HHHFNC) and maintenance intravenous fluids. The amount of fluid was decided according to clinical assessment and urine output, the aim being the prevention of hemoconcentration (due to dengue) and renal shut down (due to intravascular hemolysis). Furosemide infusion (0.05 mg/kg/hour) was administered to induce diuresis and prevent acute kidney injury (AKI) due to hemoglobinuria. Renal parameters were monitored daily and remained normal. He received a packed red blood cell transfusion on day 1 of admission, due to fall in hemoglobin that was attributed to ongoing hemolysis.

Symptomatic improvement was seen by the 4th day of admission along with normalization of the urine color, and he was weaned off from the HHHFNC. However, another blood cell transfusion was required on the 5th day of admission, due to continuous fall in hemoglobin. Subsequently, his hemogram, liver function tests, and LDH levels started to normalize [Table 1]. He remained clinically stable and was discharged on request. The child was followed up twice, on day 13 and day 21 from the day of admission. He was clinically stable and reported normal urine color. Investigation reports on the last visit were hemoglobin of 8.9 g/dl, platelets 2.45 lakhs/mm3, and LDH 511 U/L.

  Discussion Top

The patient was a 5-year-old boy with severe dengue who presented to us in the critical phase with evidence of fluid leakage as evident by pleural effusion and free fluid in the abdomen. The continuing fall in hemoglobin level without any evidence of active bleeding, indirect hyperbilirubinemia, raised LDH, hemoglobinuria, and low haptoglobin levels were suggestive of AIVH. This is commonly caused by autoimmune hemolytic anemia, falciparum malaria, ingestion of dyes, snake bites, G6PD deficiency, microangiopathic hemolytic anemia, and incompatible blood transfusions. We were able to exclude these causes by history, physical examination, and relevant laboratory examination. Thus, we attributed it to severe dengue.

Very few cases of AIVH have been reported as a complication of dengue in children. The Sri Lankan boy with massive hemoglobinuria[8] was managed with forced diuresis and isotonic saline boluses in addition to maintenance fluid therapy. The type of fluid management will depend on which phase of illness the child is in. In the critical phase, the aim should be to maintain a fine balance between extravascular fluid overload and intravascular fluid depletion due to the leaky capillaries. The use of fluids and diuretics should be balanced to maintain circulating volume and simultaneously avoiding renal shutdown. During AIVH, erythrocyte lysis releases hemoglobin which binds to haptoglobin and is reabsorbed by the kidneys. Once the haptoglobin binding capacity gets exceeded, free hemoglobin appears in the urine imparting the typical 'cola' color to it. The accumulation of excessive ferric ions causes free radical formation, damage to the tubule epithelial cells leading to renal tubular toxicity and AKI.[9] If managed appropriately, the outcome should be favorable.

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.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Gubler DJ. Dengue and dengue hemorrhagic fever. Clin Microbiol Rev 1998;11:480-96.  Back to cited text no. 1
Ghosh S, Singh R, Ghosh S, et al. Unusual surgical emergency in a patient of dengue haemorrhagic fever: Spontaneous rectus sheath haematoma leading to abdominal compartment syndrome. BMJ Case Rep 2018;2018:r-225936.  Back to cited text no. 2
Medagoda K, Gunathilaka SB, De Silva HJ. A case of self-limiting Coomb's negative haemolytic anaemia following dengue shock syndrome. Ceylon Med J 2003;48:147-8.  Back to cited text no. 3
Mahardhika GS, Tedjamartono TD, Mahendra PD. Expanded dengue syndrome with hemolytic anemia: A case report. Int Res Med Health Sci 2020;3:37-49.  Back to cited text no. 4
Aye M, Cabot J, William LW. Severe dengue fever with haemolytic anaemia – A case study. Trop Med Infect Dis 2016;1:E6.  Back to cited text no. 5
Kulkarni D, Sharma B. Dengue fever-induced cold-agglutinin syndrome. Ther Adv Infect Dis 2014;2:97-9.  Back to cited text no. 6
Radakovic-Fijan S, Graninger W, Müller C, et al. Dengue hemorrhagic fever in a British travel guide. J Am Acad Dermatol 2002;46:430-3.  Back to cited text no. 7
Sellahewa KH, Kumaratne MP, Halpe S, et al. Case report: A case of acute intravascular hemolysis in dengue fever. Am J Trop Med Hyg 2020;102:355-8.  Back to cited text no. 8
Garcia-Rubio I, Baek JH, Spahn DR, et al. Hemoglobinuria-related acute kidney injury is driven by intrarenal oxidative reactions triggering a heme toxicity response. Cell Death Dis 2016;7:e2064.  Back to cited text no. 9


  [Figure 1]

  [Table 1]


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