European Journal of Cardiovascular Medicine

Thrombocytopenia is a common occurrence in acute febrile illnesses, particularly in pediatric populations. Febrile thrombocytopenia is characterized by a platelet count of less than1,000,000 cells/cu.mm(thrombocytopenia) and coupled with fever1 . Thrombocytopenia can result from a wide range of etiologies, including infections, medications, immune disorders, and systemic diseases. In the context of infectious diseases, thrombocytopenia often serves as a crucial clinical indicator, reflecting the severity and underlying pathophysiology of the infection. Infections, such as malaria, dengue, scrub typhus, and leptospirosis, are a significant cause of febrile thrombocytopenia, with dengue being the most common infection associated with this condition. These infections are endemic in specific areas, while seasonal outbreaks occur annually in other regions.

The impact of various infectious agents on platelet counts can vary based on several factors, including the pathogenesis of the infection, host immune response, and virulence characteristics of the pathogen2. For instance, dengue virus infection typically induces transient thrombocytopenia during the febrile phase, followed by a recovery phase characterized by platelet rebound. This biphasic pattern reflects the interplay between viral replication, immune activation, and vascular leakage3. In contrast, bacterial infections such as scrub typhus and leptospirosis may elicit more profound and persistent thrombocytopenia due to systemic inflammation, endothelial injury, and disseminated intravascular coagulation (DIC)4 . The severity of thrombocytopenia in these infections often correlates with disease severity and is 3 related with adverse clinical outcomes, including multiorgan dysfunction and mortality. Parasitic infections such as malaria exhibit distinct patterns of thrombocytopenia depending on the species involved. Plasmodium falciparum, the most virulent malaria parasite, is notorious for causing severe thrombocytopenia through a combination of immune-mediated destruction and microvascular sequestration of infected erythrocytes. In contrast, Plasmodium vivax and Plasmodium ovale infections typically result in milder thrombocytopenia, often resolving spontaneously with antimalarial treatment5,6.

The typical platelet count ranges from 150000 to 450000/mm3 . Platelets play a key role in blood coagulation. Thrombocytopenia refers to a platelet count of fewer than 150,000/μl. This is related to decreased synthesis, increased destruction (both non-immunogenic and immunogenic), and greater sequestration in the spleen7. When fever is accompanied with thrombocytopenia, it can assist narrow the differential diagnosis and manage the condition.8  Patients presenting with acute febrile illness and thrombocytopenia often exhibit a spectrum of clinical manifestations ranging from mild self-limiting febrile episodes to severe, lifethreatening conditions such as hemorrhagic fever syndromes9 . Common symptoms include fever, malaise, myalgia, headache, and signs of bleeding diathesis such as petechiae, purpura, or mucosal bleeding10 . The normal Bleeding manifestations, like petechiae and purpura, are common in patients with low platelet counts. Rarely, the platelet count can be as low as 5,000/mm3 , which exposes individuals to life-threatening bleeding from the gastrointestinal and genitourinary tracts or in the central nervous system (CNS). In severe fever with thrombocytopenia syndrome (SFTS), a tick borne viral disease, patients may experience acute fever, vomiting, diarrhea, fatigue, and myalgia. SFTS can lead to hemorrhagic fever and multiple organ failure, with mortality rates varying based on the severity of the disease and timely treatment initiation.

Platelet transfusion is usually unnecessary, and good recovery is observed in the majority of cases. Immunization against vaccine-preventable diseases is highly recommended to prevent such infections11. Platelet transfusion is recommended for patients with platelet counts less than 20,000/cumm12.

Understanding the clinical and etiological profile of acute febrile illness with thrombocytopenia is essential for accurate diagnosis, timely intervention, and appropriate management. This comprehensive understanding not only aids in early identification of potentially life-threatening conditions but also guides therapeutic strategies tailored to the specific causative agents. Moreover, discerning the impact of different infectious agents on platelet counts provides valuable insights into the pathogenesis and clinical course of these infections. Therefore study title “Assessment of the Clinical and Causal Factors in Patients with Acute Febrile Illness and Low Platelet Counts at a Tertiary Care Hospital ” was conducted at Hassan Institute of Medical Sciences (HIMS), Hassan , Karnataka to evaluate the clinical and etiological profile of acute febrile illness with thrombocytopenia patients, find out the prevalence of organ specific complications in acute febrile illness with thrombocytopenia cases and determine the relationship between platelet count and bleeding manifestation according to underlying cause.

AIMS AND OBJECTIVES OF THE STUDY

1)           To evaluate the clinical and etiological profile of acute febrile illness with thrombocytopenia patients 

2)           To find out the prevalence of organ specific complications in acute febrile illness with

thrombocytopenia cases

3)           To determine the relationship between platelet count and bleeding manifestation according to underlying cause

Source of data: The cross-sectional observation study was conducted at the Department of General Medicine at Hassan Institute of Medical Sciences (HIMS), Hassan. Data were collected from all patients presenting with fever with thrombocytopenia who met the inclusion and exclusion criteria over a study period of one year.

Study Design: A cross-sectional observation study

Study Period: The study was conducted over a period of one year.

Estimation of sample size:

The sample size for the current study was calculated using following equation

𝒏=𝒁^𝟐𝑷(𝟏−𝑷)/𝒅^𝟐

Where n= sample size

Z=Z statistic for a level of confidence level at= 1.960

P=Prevalence (42.07%) d = precession (8.4%)

The prevalence of acute febrile illness with thrombocytopenia in India was found to be 42.07% as per the study by Jana et al., Therefore with p = 42.07% at 95% confidence with 85% power, the calculated sample size was 138. Hence total 140 patients (rounded off) were included in the current study according to inclusion criteria.

ADD FORMULA FROM WORD DOCUMENT

The prevalence of acute febrile illness with thrombocytopenia in India was found to be 42.07% as per the study by Jana et al., . Therefore with p = 42.07% at 95% confidence with 85% power, the calculated sample size was 138. Hence total 140 patients (rounded off) were included in the current study according to inclusion criteria.

Inclusion criteria:

All the patients (both male and female) aged ≥ 18 years had fever less than 15 days duration visited OPD, IPD, Emergency room of Hassan Institute of Medical Sciences (HIMS), Hassan were included in the study. All the patients who had Platelets count < 1.5 lakhs and gave informed consent were considered in the current study.

Exclusion criteria:

The study excluded individuals under the age of 18, those with chronic liver illness, chronic renal disease, or primary thrombocytopenia, and those who refused to provide consent. Patients, who were pregnant, had drug-induced thrombocytopenia, were diagnosed with hematological diseases or cancer, or were receiving chemotherapy or other immunosuppressive medicines were excluded from the study.

METHODOLOGY:

The study was a hospital based cross sectional study carried out in Hassan Institute of Medical Sciences (HIMS), Hassan . After obtaining approval and clearance from the institutional ethics committee , the patients fulfilling the inclusion criteria were enrolled for the study. Informed consent  were obtained from patients after explaining to them the plan and intention of the study in the language they understood. 40 Total 140 patients were included in the current study. Information regarding sociodemographic profile, clinical history was noted down in a semi-structured study proforma. Those admitted with acute febrile illness with thrombocytopenia were examined for clinical features. Detailed history was taken regarding illness in the past and diseases were confirmed by blood investigations. Every piece of information was meticulously entered into an excel spread sheet and used for statistical analysis.

Statistical Analysis:

Continuous variables were represented as mean ± SD (standard deviation) whereas categorical variable are presented as frequency and percentages (n(%)). Continuous variables were compared using independent T-test or ANOVA/ or a Kruskal-Wallis test, and categorical variables were compared using a χ2 test or fisher’s exact test to test for differences across groups. P value < 0.05 was considered statistically significant. R version 4.2.2 statistical software was used for the statistical analyses. Microsoft word and Excel was used to generate graphs, tables etc wherever require.

Table1:Grades of thrombocytopenia of patients based on age groups

Inthecurrentstudy,itwasfoundthattherewasnostatisticallysignificantdifferencein age group distribution ofpatients based on grades of thrombocytopenia with p value = 0.248 forchisquaretest(Table10).Itwasfoundthatthemaximumnumberofpatientsinalltheage groups fall under mild thrombocytopenia than of any other grades of thrombocytopenia. 5(45.46),24(58.54), 38(62.30)and 19(70.37)patient in theagegroups ≤ 20, >20≤40, >40≤60 and >60 years respectively had mild thrombocytopenia.Age group distribution based the grades of thrombocytopenia is graphically illustrated.

Table 2: Etiology of fever with thrombocytopenia

Out of 140 cases with fever and thrombocytopenia, 80 (57.14%) were diagnosed with denguefever,followedbyRickettsia(22.14(22.14%)),Leptospirosis(14(10%)),Viralinfection (10(7.1%)), andunexplained (9(6.43%))

Table 3: Clinical features distribution based on age groups

Age group distribution of patients with thrombocytopenia based on symptomatic manifestation. It was foundthat statically suggestive significance was found for the age group wise distribution with mayalgia and altered sensorium for chi-square test. Mayalgia was found in maximum patients (90%) in age group>40≤60whereasalteredsensoriumwasfoundmorepeople (22%)withagegroup >60. For rest of the symptoms there was no statically significant difference was found between different age groups.

Table 4: Association of Diseases with clinical features of study population

Distribution of symptomatic manifestation with respect to the aetiology of thrombocytopeniawasstudiedinthecurrentstudy.Itwasfoundthat staticallysignificancewasfoundonlyforthesymptompaininabdomen. Paininabdomenwas foundinmaximumpatients (56.25%) withdenguethanwithanyotherdiseaseswithpvalue

=0.027 for chi-square test. For rest of the symptoms there was no statically significant difference was found between different etiologies of thrombocytopenia.

Table 5:USG Abdomen and Pelvis and clinical features

Associationbetweensymptomsandtheultrasoundfindingwasstudiedinthecurrentstudy. There was statistically significant difference of distribution of stones in gallbladder, asicties and pleural effusion with respect to rashes. 31(81.58%), 16(48.48%) and 12(41.38%) patients with rashes respectively had stones in gallbladder, asicties and pleural effusion.

Acute febrile illnesses (AFIs) are common clinical conditions characterized by a sudden onset of fever and various accompanying symptoms. They encompass a wide spectrum of diseases, ranging from self-limiting viral infections to life-threatening bacterial, parasitic, or viral diseases. Thrombocytopenia, defined as a platelet count below 150,000 per microliter of blood, frequently accompanies these illnesses13. The co-occurrence of fever and thrombocytopenia can complicate the clinical picture, making diagnosis and management challenging. Thrombocytopenia in the context of acute febrile illness can be indicative of several serious underlying conditions, such as dengue fever, malaria, leptospirosis, rickettsial infections, and bacterial sepsis, among others. Each of these conditions necessitates a specific diagnostic approach and treatment protocol. Failure to correctly identify the etiology can lead to inappropriate management, potentially resulting in severe complications or death14. Since acute febrile illness with thrombocytopenia is primarily caused by a limited number of etiological agents, which can be identified through a structured clinical and laboratory evaluation, leading to targeted and effective management strategies The current cross-sectional study “Assessment of the Clinical and Causal Factors in Patients with Acute Febrile Illness and Low Platelet Counts at a Tertiary Care Hospital ” was carried out at Hassan Institute of Medical Sciences (HIMS), Hassan, Karnataka. The purpose of this study was to assess the clinical and etiological profile of patients with acute febrile illness and thrombocytopenia, as well as to ascertain the association between bleeding manifestation and platelet count in relation to the underlying cause and the prevalence of organspecific complications in cases of acute febrile illness and thrombocytopenia.

In the current study total 140 acute febrile illness patients with thrombocytopenia were considered based on inclusion and exclusion criteria. The study consisted of 63 females (45%) and 77 males (55%). In the study of adult patients with febrile thrombocytopenia conducted by  Patil and Chhajed, 109 (59%) were males and 75 (41%) were females. Dev et al., found that out of 350 patients in their study, 54.3% were male and 45.7% were female. Study by Dhunputh et al in Assam reported male 112 cases (57.14%) and females were 84 cases (42.86%)15. Jain et al., reported of 67 (56.7%) males and 51 (43.3%) females out of 118 patients in their study where as et al., reported that there were 91 (56.88%) males and 69(43.12%) females out of 160 patients in their study. Our study population was fairly balanced in terms of gender, suggesting that acute febrile illness and thrombocytopenia can affect both genders equally.

The mean age of patients in the current study was recorded as 44.89±17.40 years, with a significant prevalence (43.7%) in the 40-60 year age group. Age-specific risk factors were highlighted, aligning with findings from other studies. For instance, a study on febrile neutropenia in adults with diffuse large B-cell lymphoma reported a median age of 60 years at diagnosis, while another study found the highest prevalence in the 19-30 year group (30%), followed by 31-40 years (25%) and 41-50 years (21%). Sumagala et al. reported that febrile thrombocytopenia affected a broad age range (18-75 years), but was most common in the 21- 30 year group (40.60%). Similarly, Radhika et al. observed that the majority of cases occurred in individuals aged 18 to 40 years. Gondhali et al. found the highest prevalence (32%) in the 21-30 year group. These findings suggest that younger adults, particularly those aged 21-30, are at higher risk, possibly due to factors such as outdoor work and sleeping habits that increase exposure to mosquito bites, a common vector for febrile illnesses16.

In the current study tachycardia was observed in 30 patients whereas blood pressure anomalies were minimal, with only 5% (7 patients) hypertensive and 12% (17 patients) hypotensive. The prevalence of tachycardia, hypertensive, and hypotensive symptoms in acute febrile illness patients with thrombocytopenia varies across studies. Study by Gnanamuthu et al., with 180 patients reported that a total 10.5% had tachycardia with 26.5% hypotensive and only 5% hypertensive. These findings are consistent with other studies, though variations exist. 76 For instance, Gnanamuthu et al. reported a lower prevalence of tachycardia (10.5%) and a higher incidence of hypotension (26.5%) among 180 patients, with only 5% hypertensive. This variability suggests that while tachycardia and blood pressure anomalies are common in patients with acute febrile illness and thrombocytopenia, the prevalence rates can differ significantly across studies and populations. The progression of the disease often leads to cardiac dysfunction, which is reflected in several studies examining severe fever with thrombocytopenia syndrome (SFTS). Li et al. analyzed 2,096 SFTS patients and found no cardiac abnormalities, though elevated creatine kinase (CK) levels were noted in deceased patients compared to survivors. This contrasts with a retrospective review of 115 hospitalized SFTSV patients, where 23.6% showed arrhythmias, and 58.1% of those tested had elevated troponin levels. Additionally, elevated cardiac biomarkers such as CK, CK-MB, and LDH were detected in over 70% of patients, indicating a high prevalence of myocardial damage.

A normal human platelet count ranges from 1,50,000 to 4,50,000 platelets/µL of blood. Thrombocytopenia is defined as a subnormal number of platelets in the circulating blood, typically less than 50,000/µL. Severe thrombocytopenia is characterized by a platelet count less than 10,000/µL, which is rare and potentially fatal due to bleeding complications. Thrombocytopenia is a common feature in patients with acute febrile illness. The mean lowest platelet count in the current study was 70,514±36,642.84 cells/mm³. Thrombocytopenia severity varied, with 86 patients (61.43%) classified as mild, 48(34.29%) as moderate, and 6(3.33%) as severe. Different studies have reported varying ranges of platelet counts in these patients, reflecting the diverse aetiologies and severities of the condition. In a study on clinical, haematological, and biochemical profiles in acute febrile illnesses with thrombocytopenia, the platelet count distribution was as follows: 6 patients (3%) had platelets less than 10,000/µL, 48 patients (24%) had platelets between 10,000-20,000/µL, and 146 patients (73%) had platelets more than 20,000/µL86 . Gnanamuthu et al. in their study Involving 180 patients, reported 77 thrombocytopenia with platelet counts ranging from 20,000 to 100,000/µL, where 2 patients (1%) had platelets less than 10,000/µL, 48 patients (27%) had platelets between 10,000- 20,000/µL, and 54 patients (30%) had platelets less than 20,000/µL. Choudhary et al., in their study found that 6 patients (3%) had platelets less than 10,000/µL, 48 patients (24%) had platelets between 10,000-20,000/µL, and 146 patients (73%) had platelets more than 20,000/µL. Dev et al., reported that thrombocytopenia was observed in all the patients in their study with 65% patients having plates below 50,000/µL.These studies collectively illustrate that thrombocytopenia in acute febrile illness can present with platelet counts ranging from mildly reduced levels to severe thrombocytopenia, often below 50,000/µL. The variability in platelet counts is influenced by factors such as the underlying cause of the febrile illness, the severity of the infection, and the patient's overall health status.

A normal human platelet count ranges from 1,50,000 to 4,50,000 platelets/µL of blood. Thrombocytopenia is defined as a subnormal number of platelets in the circulating blood, typically less than 50,000/µL. Severe thrombocytopenia is characterized by a platelet count less than 10,000/µL, which is rare and potentially fatal due to bleeding complications. Thrombocytopenia is a common feature in patients with acute febrile illness. The mean lowest platelet count in the current study was 70,514±36,642.84 cells/mm³. Thrombocytopenia severity varied, with 86 patients (61.43%) classified as mild, 48(34.29%) as moderate, and 6(3.33%) as severe. Different studies have reported varying ranges of platelet counts in these patients, reflecting the diverse aetiologies and severities of the condition. In a study on clinical, haematological, and biochemical profiles in acute febrile illnesses with thrombocytopenia, the platelet count distribution was as follows: 6 patients (3%) had platelets less than 10,000/µL, 48 patients (24%) had platelets between 10,000-20,000/µL, and 146 patients (73%) had platelets more than 20,000/µL. Gnanamuthu et al. in their study Involving 180 patients, reported 77 thrombocytopenia with platelet counts ranging from 20,000 to 100,000/µL, where 2 patients (1%) had platelets less than 10,000/µL, 48 patients (27%) had platelets between 10,000- 20,000/µL, and 54 patients (30%) had platelets less than 20,000/µL. Choudhary et al., in their study found that 6 patients (3%) had platelets less than 10,000/µL, 48 patients (24%) had platelets between 10,000-20,000/µL, and 146 patients (73%) had platelets more than 20,000/µL23 . Dev et al., reported that thrombocytopenia was observed in all the patients in their study with 65% patients having plates below 50,000/µL.These studies collectively illustrate that thrombocytopenia in acute febrile illness can present with platelet counts ranging from mildly reduced levels to severe thrombocytopenia, often below 50,000/µL. The variability in platelet counts is influenced by factors such as the underlying cause of the febrile illness, the severity of the infection, and the patient's overall health status.

All patients in the current study presented with fever, accompanied by common symptoms such as headache (85%), body ache (84.29%), vomiting (75%), abdominal pain (50%), altered sensorium (10.71%), and bleeding manifestations (5.7%). Physical examinations showed rashes in 37.86% and breathlessness in 15% of patients. Notably, severe thrombocytopenia was associated with a higher incidence of rashes (66%) and bleeding manifestations (50%). The severity of thrombocytopenia correlates directly with the risk of bleeding complications. Patients with severe thrombocytopenia (platelet count)

Biochemical tests play a pivotal role in understanding the clinical and etiological profiles of patients suffering from acute febrile illness with thrombocytopenia. Blood urea and serum creatinine levels are critical indicators of kidney function, particularly in patients with AFI and thrombocytopenia. The study findings indicate a significant correlation between the severity of thrombocytopenia and elevated levels of these renal markers. Patients classified with severe thrombocytopenia exhibited substantially higher mean blood urea and serum creatinine levels compared to those with mild or moderate thrombocytopenia (p-value = 0.041). This suggests that severe thrombocytopenia might be associated with more pronounced renal impairment. Comparatively, in the study by Negi et al., derangements in renal function tests were observed in a notable proportion of patients, with serum creatinine and urea abnormalities present in 24% and 16% of cases, respectively. The most prevalent etiologies linked with renal dysfunction included malaria (40%), scrub typhus (38.88%), septicemia (33.33%), undiagnosed cases (27.27%), and dengue fever (7%). Similarly, Gondhali et al. reported that 24% of the cases exhibited abnormal renal function tests, predominantly in patients with septicemia, followed by dengue, malaria, and viral hepatitis17.

Liver function tests, including total bilirubin, SGOT, and SGPT, are essential in assessing hepatic involvement in AFI with thrombocytopenia. This study demonstrated that patients with severe thrombocytopenia had significantly higher mean total bilirubin levels and SGOT compared to those with milder forms of thrombocytopenia. This elevation in liver enzymes and bilirubin levels indicates potential liver damage or dysfunction associated with the severity of thrombocytopenia. In the study by Negi et al., liver function test abnormalities were common, with SGPT, SGOT, and serum bilirubin derangements observed in 47%, 43%, and 15% of patients, respectively. The most frequent causes of abnormal liver function were 80 malaria (63.33%), scrub typhus (55.55%), septicemia (50%), dengue (34.14%), undiagnosed cases (27.27%), and typhoid fever (20%). Gondhali et al. reported similar findings, with 56 cases of dengue fever showing 3 cases with abnormal total bilirubin, 17 cases with abnormal SGOT, and 13 cases with abnormal SGPT levels. Additionally, in 15 cases of malaria, 11 had abnormal total bilirubin, 7 had abnormal SGOT, and 3 had abnormal SGPT levels. All cases of septicemia and viral hepatitis exhibited abnormal liver function tests18.

The prevalence of gallbladder stones in patients with acute febrile illness and thrombocytopenia was 22.14%, significantly higher in males (31.17%) than females (11.11%) (p=0.05). Gallbladder stones are typically associated with risk factors such as obesity, age, gender (more common in females), and specific conditions like hemolytic diseases. The higher incidence in males observed in this study is contrary to general population trends, where females are usually more affected. This discrepancy could be due to the specific population studied (acute febrile illness with thrombocytopenia), which might have unique pathophysiological processes. For instance, conditions like dengue and leptospirosis, which can lead to acute febrile illnesses and thrombocytopenia, may contribute to the formation of gallbladder stones differently in males and females.

Ascites was present in 22.57% of patients, with a significant gender difference: 42.86% in males and 0% in females (p< 0.0001). Ascites is often seen in severe liver diseases, heart failure, or infections like tuberculosis. Its occurrence in febrile illnesses can indicate severe systemic involvement. The marked gender difference in this study suggests males with acute febrile illnesses and thrombocytopenia might have more severe systemic or hepatic involvement leading to ascites. Previous studies, such as those on dengue, have reported ascites as a common complication, particularly in severe cases, but have not consistently shown a gender difference.

Pleural effusion was observed in 20.71% of patients, more frequently in males (32.47%) than females (6.35%) (p=0.0002). Pleural effusion in febrile illnesses can result from inflammation, infection, or systemic disease processes like those seen in severe dengue or leptospirosis. The gender disparity seen here, with males more frequently affected, could point to differences in disease severity or immune response between genders. Studies on diseases like dengue have documented pleural effusion but without significant gender-based differences19.

In the current study, severe thrombocytopenia was strongly associated with higher incidences of gallbladder stones (66.67%), ascites (66.67%), and pleural effusion (50%) compared to moderate and mild cases. The association between severe thrombocytopenia and increased risk of organ-specific complications is well-documented. For example, in dengue fever, severe thrombocytopenia often correlates with plasma leakage, leading to complications such as ascites and pleural effusion. This study aligns with findings from previous research, emphasizing the importance of monitoring and managing severe thrombocytopenia to prevent these complications. However, the specific link to gallbladder stones is less commonly reported, suggesting a need for further investigation into the pathophysiological mechanisms in this subset of patients.

This study provides a comprehensive overview of the clinical and etiological profiles of patients with acute febrile illness (AFI) accompanied by thrombocytopenia, conducted at Hassan Institute of Medical Sciences (HIMS), Hassan . Our findings emphasize the complexity and variability of AFI with thrombocytopenia, highlighting the necessity for detailed clinical and biochemical assessments to accurately diagnose and manage these conditions. The study emphasizes the critical need for early and accurate diagnosis through structured clinical and laboratory evaluations. Recognizing the specific etiological agents and understanding the associated biochemical derangements can guide targeted treatment strategies, ultimately improving patient outcomes. Given the regional variability in the causes of AFI with thrombocytopenia, healthcare providers should tailor their diagnostic and therapeutic approaches based on the local epidemiological profile.

The study included a balanced gender distribution with a slight male predominance (55% males vs. 45% females). The mean age of the patients was 44.89 years, with the highest prevalence in the 40-60 year age group. This aligns with other studies indicating that AFI with thrombocytopenia affects a wide age range but is particularly prevalent among younger adults due to factors such as increased exposure to vectors. Common symptoms included fever, headache, body ache, vomiting, and abdominal pain. Severe thrombocytopenia was notably associated with higher incidences of rashes and bleeding manifestations, reflecting the direct correlation between thrombocytopenia severity and bleeding risk. The study categorized patients into mild, moderate, and severe thrombocytopenia, with the majority having mild thrombocytopenia. Severe cases, although less frequent, were significantly associated with higher risks of bleeding and organ-specific complications. Elevated blood urea and serum creatinine levels were significantly associated with severe thrombocytopenia, indicating potential renal impairment. Liver function tests also showed significant abnormalities in severe 84 thrombocytopenia cases, suggesting hepatic involvement. The most common etiological agents identified were dengue fever (57.14%), followed by Rickettsia, leptospirosis, viral infections, and unexplained cases. This distribution underscores the regional variations in the causes of AFI with thrombocytopenia, with vector-borne diseases being predominant. Ultrasound imaging revealed gallbladder stones, ascites, and pleural effusion, particularly in patients with severe thrombocytopenia. These findings highlight the potential for significant organ involvement and complications in severe cases.

In conclusion, this study highlights the multifaceted nature of acute febrile illness with thrombocytopenia and the importance of a thorough clinical and biochemical evaluation to improve diagnosis, management, and patient outcomes.

1. K,J.JR,R.V.J,KuttuvaS.Spectrumoffebrilethrombocytopeniaamongchildrenina tropicalcountry-ahospitalbasedobservationalstudyinSouthIndia.IntJContempPediatr. 2021;8(2):354. doi:10.18203/2349-3291.ijcp20210128
2. Yeaman MR. Platelets in defense against bacterial pathogens. Cell Mol Life Sci. 2010;67(4):525-544. doi:10.1007/s00018-009-0210-4
3. Azeredo ELD, Monteiro RQ, de-Oliveira Pinto LM. Thrombocytopenia in Dengue: Interrelationship between Virus and the Imbalance between Coagulation and Fibrinolysis and Inflammatory Mediators. Mediators of Inflammation. 2015;2015:1-16. doi:10.1155/2015/313842
4. Ittyachen AM, Abraham SP, Krishnamoorthy S, Vijayan A, Kokkat J. Immune thrombocytopenia with multi-organ dysfunction syndrome as a rare presentation of scrub typhus: a case report. BMC Res Notes. 2017;10(1):496. doi:10.1186/s13104-017-2826-z
5. Gebreweld A, Erkihun Y, Feleke DG, Hailu G, Fiseha T. Thrombocytopenia as a DiagnosticMarkerforMalariainPatientswithAcuteFebrileIllness.TomaA,ed.Journal of Tropical Medicine. 2021;2021:1-6. doi:10.1155/2021/5585272
6. Laishram DD, Sutton PL, Nanda N, et al. The complexities of malaria disease manifestations with a focus on asymptomatic malaria. Malar J. 2012;11(1):29. doi:10.1186/1475-2875-11-29
7. Gaikwad DD, Kar A. Clinical and etiological profile of acute febrile illness with thrombocytopenia. MIJOMED. 2021;20(1):19-22. doi:10.26611/10212014
8. Negi A, Singh Y, Singh M, Saxena SR. A Study of Acute Febrile Illness with Thrombocytopenia from Tertiary Care Centre of Uttarakhand. Annals of International Medical and Dental Research. 2018;4(3):2395-2814.
9. ViralFebrileIllnessesandEmergingPathogens.In:Hunter’sTropicalMedicine and Emerging Infectious Diseases. Elsevier; 2020:325-350. doi:10.1016/B978-0-323- 55512-8.00036-3
10. IbaT,LevyJH,LeviM.Viral-InducedInflammatoryCoagulationDisorders:Preparingfor Another Epidemic. Thromb Haemost. 2022;122(01):008-019. doi:10.1055/a-1562-7599
11. Choudhary MK, Mishra AK, Kumar P, et al. Study of the Aetiology and Clinical Manifestations of Thrombocytopenia in a Tertiary Care Centre. Cureus. Published online July 7, 2023. doi:10.7759/cureus.41511
12. Kayal L, Jayachandran S, Singh K. Idiopathic thrombocytopenic purpura. Contemp Clin Dent. 2014;5(3):410. doi:10.4103/0976-237X.137976
13. V R, C.S. S, Kamath V. A Study of Febrile Thrombocytopenia. IJCMR. 2019;6(9). doi:10.21276/ijcmr.2019.6.9.20
14. GondhaliMP,VethekarM,BhangaleD,ChoudharyK,ChaudharyM,KundgirA.Clinical assessmentoffeverwiththrombocytopenia-Aprospectivestudy.IntJMedRes&Health Sc. 2016;5(1):258-277.
15. Gnanamuthu S, . B, S. R. V, et al. Cardiac involvement in adult patients with febrile thrombocytopenia diagnosed by bedside 2-D echocardiography. Int J Adv Med. 2018;5(4):1016. doi:10.18203/2349-3933.ijam20183139
16. LiH,LuQB,XingB,et al.Epidemiologicalandclinicalfeaturesoflaboratory-diagnosed severe fever with thrombocytopenia syndrome in China, 2011–17: a prospective observational study. The Lancet Infectious Diseases. 2018;18(10):1127-1137. doi:10.1016/S1473-3099(18)30293-7
17. Deng B, Zhou B, Zhang S, et al. Clinical Features and Factors Associated with Severity and Fatality among Patients with Severe Fever with Thrombocytopenia Syndrome BunyavirusInfectioninNortheastChina.BauschDG,ed.PLoSONE.2013;8(11):e80802. doi:10.1371/journal.pone.0080802
18. Bhatnagar DrM, Yadav DrSK, Senior Resident, Medicine, Lady Hardinge Medical College,NewDelhi.,JagdishDRK,AssitantProfessorMedicine,SantoshMedicalCollege &Hospital,Ghaziabad.Clinical,HaematologicalandbiochemicalProfileinAcuteFebrile Illnesses with Thrombocytopenia. IJMSCI. Published online October 11, 2016. doi:10.18535/ijmsci/v3i10.03
19. GutthiLP,VegesnaS,PundarikakshaV,KollaS,GundapaneniM,KarimiPK.AStudyof Clinical and Lab Profile of Fever with Thrombocytopenia. 2015;4(5)..