Dengue fever is a mosquito-borne viral infection caused by the dengue virus (DENV), a single-stranded RNA virus belonging to the Flaviviridae family. It is transmitted to humans mainly through the bite of infected Aedes aegypti and Aedes albopictus mosquitoes.¹ Over the last decade, India has experienced a substantial increase in dengue cases, accounting for nearly 34% of global dengue infections by 2010. This surge is attributed to factors such as rapid urbanization, unplanned population growth, inadequate vector control measures, climate change, and poor sanitation. Recent years have shown not only larger and more frequent outbreaks but also an alarming shift in transmission patterns, extending from urban to semi-urban and rural areas. Consequently, the incidence of severe dengue and the case fatality rate (CFR) have increased, with national averages around 1% and higher rates of up to 3–5% in areas with limited healthcare access.²There are four antigenically distinct serotypes of the dengue virus—DENV-1, DENV-2, DENV-3, and DENV-4—all capable of causing a broad clinical spectrum ranging from asymptomatic infection to severe, life-threatening disease. The clinical course of dengue typically progresses through three distinct phases: the febrile, critical, and convalescent phases. The febrile phase, lasting 2–7 days, presents with high-grade fever, severe headache, retro-orbital pain, myalgia, arthralgia, and sometimes a transient maculopapular rash.³ The critical phase, occurring between days 3 and 8 of illness, is marked by increased capillary permeability, plasma leakage, and the potential development of dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). The convalescent phase involves gradual recovery as plasma leakage subsides and extravascular fluid is reabsorbed.The underlying pathophysiological hallmark of severe dengue is increased capillary permeability due to immune-mediated endothelial injury. This results in plasma leakage, hemoconcentration, thrombocytopenia, and bleeding tendencies. Dengue should be suspected in patients with an acute febrile illness of 2–7 days duration, accompanied by symptoms such as headache, retro-orbital pain, myalgia, arthralgia, rash⁴, or bleeding manifestations. Laboratory findings commonly include leukopenia, thrombocytopenia (platelet count <150,000/μL), and elevated liver transaminases. Thrombocytopenia arises from bone marrow suppression and peripheral platelet destruction, contributing to hemorrhagic complications in DHF and DSS.An increasingly recognized biochemical marker in dengue infection is hyperferritinemia, defined as serum ferritin levels ≥500 µg/L. Ferritin, an intracellular iron-storage protein, also functions as an acute-phase reactant released by activated macrophages and reticuloendothelial cells during inflammation.^5,6 In dengue, elevated ferritin levels reflect the extent of immune activation and systemic inflammation, correlating strongly with disease severity, hepatic dysfunction, coagulopathy, and thrombocytopenia. The pathophysiology involves overproduction of pro-inflammatory cytokines such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ), which stimulate ferritin synthesis and contribute to endothelial injury and coagulation abnormalities⁷.Markedly elevated ferritin levels have been associated with macrophage activation syndrome (MAS) and hemophagocytic lymphohistiocytosis (HLH)—hyperinflammatory states leading to cytokine storm and multi-organ involvement. Studies have consistently shown significantly higher ferritin levels in severe dengue compared to non-severe cases, making ferritin a valuable prognostic biomarker. Moreover, ferritin elevation parallels hepatic transaminase rise, linking it with liver dysfunction and hemostatic imbalance⁸. Therefore, regular monitoring of ferritin levels in dengue patients, especially those with thrombocytopenia and deranged liver enzymes, provides a simple yet effective tool for early detection of severe disease progression and timely therapeutic intervention.⁹

AIM

To assess the correlation of hyperferritinemia with thrombocytopenia among  patients of dengue fever admitted in a tertiary medical college hospital

This was a hospital-based cross-sectional study conducted in the Department of Paediatrics, Sardar Patel Medical College and P.B.M. Hospital, Bikaner. The study was carried out over a period of six months, from September 2020 to February 2021. The study population comprised children admitted to the paediatric ward with a confirmed diagnosis of dengue fever. All patients were evaluated based on the World Health Organization (WHO) criteria for dengue fever, which include acute febrile illness accompanied by symptoms such as headache, myalgia, arthralgia, rash, and bleeding manifestations.Children between 0 to 14 years of age who tested positive for either dengue NS1 antigen or IgM dengue antibody by ELISA technique were included in the study. These diagnostic methods ensured accurate identification of acute dengue infection, helping to exclude cases of past or secondary infections.Certain groups were excluded from the study to avoid confounding factors that could interfere with clinical or laboratory findings. The exclusion criteria included patients who were positive for IgG dengue antibodies, indicating past infection, as well as those diagnosed with other febrile illnesses such as malaria or enteric fever. Children with known platelet or hematological disorders, or those receiving steroid or other immunosuppressive therapy prior to admission, were also excluded. In addition, patients who left the hospital against medical advice or whose guardians refused to give consent for participation were not included in the study.

Table 1: AGE DISTRIBUTION OF PATIENTS

The age of patients ranged from 1-to 14 years. The mean age was 7.02 ± 3.07 years. Out of 150 total cases, the most commonly encountered age group was between 6-11 years in 52% cases, This was followed by 1-5 years involving 32.67% and 11-14 years involving 15.33% cases.

Table 2: DENGUE CASE SEVERITY CLASSIFICATION

In our study, dengue severity was classified using a two-step approach involving WHO 2009 criteria, ICU admission status, and verification by two independent paediatricians. Based on this, 52% of patients had non-severe dengue, while 48% had severe dengue.

Table 3: MANIFESTATIONS OF SEVERE DENGUE

Bleeding manifestations in the form of hematemesis, hematuria, purpura, epistaxis, and subconjunctival haemorrhage were the most common complication of severe dengue seen in 52% of cases. Other manifestations of severe dengue-like respiratory distress with fluid accumulation were present in 18%, dehydration in 20%, and shock in 2.67% cases. Most of the patients had more than one complication.

Table 4:BLEEDING MANIFESTATIONS IN SEVERE DENGUE

Bleeding manifestations as a sign of severe dengue were present in 78 (52%) cases. The most common manifestation was purpura and petechiae seen in 57 cases, followed by epistaxis seen in 22 cases, hematemesis  15 cases, melena in 13, hematuria in 8, and subconjunctival haemorrhage in 7 cases. Most of the cases had more than one manifestation of bleeding disorder.

Table 5:MEAN SERUM FERRITIN OF PATIENTS ACCORDING TO DISEASE SEVERITY

The mean value of serum ferritin in non-severe dengue on day 1 and day 3 was 575.88 ± 205.71 ng/ml and 405.97± 189.47 ng/ml, respectively.  While the mean value of serum ferritin in severe dengue on day 1 and day 3 was 830.06 ± 304.79 ng. ml and 801.55 ± 228.53 ng/ml, respectively. The difference between the two groups was highly statistically significant (p-value <0.001) with severe dengue having significantly higher serum ferritin levels both at admission and on day 3. 

Table 6:BASELINE DAY 1 AND DAY 3 INVESTIGATIONS OF PATIENTS

In our study, there was a statistically significant rise in total leukocyte count (p=0.03) and a highly significant increase in mean platelet volume (p<0.001) from day 1 to day 3. The rise in haemoglobin was not statistically significant (p=0.26), while hematocrit showed a highly significant fall (p<0.001). These findings indicate dynamic hematological changes during the course of dengue infection.

Table 7:PLATELET COUNT OF PATIENTS ON DAY 1 AND DAY 3

The platelet count of patients on day 1 ranged from 1,100 to 98,000/ microL with mean platelet count was 52,954 ± 27,047.44/ microL. The maximum number of patients had platelet count between 50,000-80,000 in 35.33% of cases.

The platelet count of patients on day 3 ranged from 1,700 to 99,000/ microL with mean platelet count was 54,252 ± 27,171.31/microL. Maximum number of patients had platelet count between 50,000-80,000 in 30.67% cases.

Table 8- MEAN PLATELET COUNT OF PATIENTS ACCORDING TO DISEASE SEVERITY

The mean platelet count of patients having non-severe disease on day 1 and day 3 was 79,693 ± 29,348/microL and 81,368± 45,176/microL. While the mean platelet count of patients having severe disease on day 1 and day 3 was 23,986 ± 12,031/microL and 24,876±13,091/microL respectively.  The difference in mean platelet count of patients having severe disease compared to those who had the non-severe disease was statistically significant on both day 1 and day 3 (p-value- 0.002 and 0.0003,

respectively).

Figure 1,2:CORRELATION BETWEEN SERUM FERRITIN AND PLATELET COUNT ON DAY 1 and  ON DAY 3

There was a negative correlation between platelet count and serum ferritin in patients on day 1 with the correlation coefficient being R= -0.89. The correlation was highly statistically significant with a fall in platelet count associated with a rise in serum ferritin levels. There was a negative correlation between platelet count and serum ferritin in patients on day 3 with the correlation coefficient being R= -0.61. The correlation was statistically significant with a fall in platelet count associated with a rise in serum ferritin levels.

The age of patients in our study ranged from 1-14 years. The mean age was 7.02 ± 3.07 years. Out of 150 total cases, the most commonly encountered age group was between 6-11 years in 52% cases, This was followed by 1-5 years involving 32.67% and 11-14 years involving 15.33% cases. However, the age distribution of patients in Aashiq et al's¹⁰ study was similar to ours with the mean age of the study population being 8.51±3.5 years. But their sample size was a lot smaller with only 58 children being included.

 Out of 150 patients, 52% of patients had non-severe dengue, and 48% of patients had severe dengue.

The mean platelet count of patients in our subjects having nonsevere disease on day 1 and day 3 was 79,693 ± 29,348/microL and  81,368± 45,176/microL. While the mean platelet count of patients having severe disease on day 1 and day 3 was 23,986 ± 12,031/microL and 24,876±13,091/microL respectively. The difference in mean platelet count of patients having severe disease compared to those who had the non-severe disease was statistically significant on both day 1 and day 3 (p-value- 0.002 and 0.0003, respectively).

In our study, bleeding manifestations in the form of hematemesis, hematuria, purpura, epistaxis, and subconjunctival haemorrhage were the most common complication of severe dengue seen in 52% of cases. Other manifestations of severe dengue-like respiratory distress with fluid accumulation were present in 18%, dehydration in 20%, and shock in 2.67% cases. Most of the patients had more than one complication. In a study conducted by Pone et al.,¹¹ similar observations were made with 65.2% having bleeding manifestations.

However, the clinical features of thrombocytopenia in our study were more than that reported by other authors like Sriram Pothapregada et al.¹² In their study hemorrhagic manifestations were present in 52 children (19.9%), which mainly included skin bleeding (39.2%), gum bleeding (34.6%), epistaxis (23.1%), melena (26.9%), hematemesis (9.6%), intracranial bleed (3.8%), and pulmonary bleed (7.7%). The tourniquet test was positive in 33 cases (12.6%). Melena was the most common form of gastrointestinal (GI) bleed.90

We also observed that the mean value of serum ferritin in nonsevere dengue on day 1 and day 3 were 575.88 ± 205.71 ng/ml and 405.97± 189.47 ng/ml, respectively. While the mean value of serum ferritin in severe dengue on day 1 and day 3 was 830.06 ± 304.79 ng/ml and 801.55 ± 228.53 ng/ml, respectively. The difference between the two groups was highly statistically significant (p-value <0.001) with severe dengue having significantly higher serum ferritin levels both at admission and on day 3. 

In the present study, we found that a higher serum ferritin level during the febrile phase is significantly associated with a lower platelet count during a critical period of dengue fever. which ultimately correlates with the severity of the disease. Similar findings were noted in other studies as well. Recently published another study by Petchiappan et al.¹⁴ (2019) from Tamilnadu, India also described similar observations in 119 patients with dengue fever.

In our study, we observed that there was a negative correlation between platelet count and serum ferritin in patients on day 1 with the correlation coefficient being R= -0.89. The correlation was highly statistically significant with a fall in platelet count associated with a rise in serum ferritin levels.

There was a negative correlation between platelet count and serum ferritin in patients on day 1 with the correlation coefficient being R= -0.61. There was a negative correlation between platelet count and serum ferritin in patients on day 3 with the correlation coefficient being R= -0.61. The correlation was statistically significant with a fall in platelet count associated with a rise in serum ferritin levels. These findings were in close approximation with Ahmed et al.'s¹⁴ who also found a negative correlation of serum ferritin and lowest platelet count. The Pearson correlation value was – 0.348. The result was statistically significant (p=0.05).

Dengue is a serious infection that can range from mild illness to severe life-threatening complications like DSS/DHF. In this period of dilemma in the clinicians' front, ferritin was evaluated as an adjunct marker for the diagnosis of dengue which could aid their clinical judgement and prompt early fluid resuscitation which in turn could be useful in avoiding undue complications. Ferritin, as evaluated in the present study may serve as a significant marker for differentiating between non-severe dengue cases and severe dengue cases.

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