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A study of clinical profile of patients with dengue fever with thrombocytopenia authors

 

Nikhil A Kharat1*, R B Kulkarni2

 

1Junior Resident, Medicine Department, Bharati Vidyapeeth Deemed University, Medical College and Hospital, Sangli, Maharashtra, INDIA.

2 Professors of Medicine and Dean, Bharati Vidyapeeth Deemed University Medical College and Hospital, Sangli, Maharashtra, INDIA.

Email: nikofgmc@gmail.com

 

Abstract          Objective: Recently there is increased incidence of Dengue fever in urban as well as rural area which is associated with loss of working days, morbidity and mortality. There are generalized misconceptions about thrombocytopenia-platelet transfusion-outcome of disease. Hence we decided to take this study. Materials and Methods: A prospective study was conducted in our hospital in medicine department from 1st Jan2012 to 31st Dec 2012. Various factors like age, symptoms, hematocrit, platelet count, liver and renal function tests, third space loss, presence or absence of shock, outcome in relation to shock and platelet transfusion were studied independently and in association with each other. Data was collected, tabulated and analyzed. Results: Presence of shock at time of admission was an important factor contributing to hemorrhage in Dengue Hemorrhagic Fever. No association between platelet count and hematocrit at time of admission and outcome of the disease. Insignificant P value(0.129) for platelet transfusion and overall outcome in patients. Positive association of shock with third space loss of fluid. Significant association of shock with mortality. Conclusion: Main factor contributing to mortality was presence of shock, hence shock should be corrected rapidly with careful I.V. administration to prevent tissue hypoxia and organ dysfunction. Platelet count does not correlate with severity and mortality of the disease. Prophylactic transfusions are unnecessary. Platelet transfusion may benefit the patient with thrombocytopenia and hemorrhage which continues despite blood transfusion.

Keywords: dengue fever, thrombocytopenia.

 

INTRODUCTION

Dengue is a mosquito borne Arboviral disease caused by the dengue virus. The global prevalence has grown dramatically in the recent decades1.The first evidence of Dengue Fever in India was reported during 1956 from Vellore District in Tamil Nadu3. Since then, numerous outbreaks of Dengue Fever/Dengue Hemorrhagic Fever have been reported from various states in India. In 2012 Maharashtra had 2931 cases with 59 deaths6. Initially outbreak was in few districts of Maharashtra. But recently fresh epidemics of dengue in almost each and every districts of Maharashtra have broken out. The dengue virus is transmitted by the Aedes Aegypti mosquito. Since Aedes Aegypti breeding is more common in urban areas, the disease was prevalent in urban areas. However, the trend is now changing due to socio economic and manmade ecological changes leading to spread of dengue in rural areas. For a disease that is complex in its manifestations, management is relatively simple, inexpensive and very effective in saving lives.

 

PURPOSE OF STUDY

Incidence of Dengue is Maximum in Maharashtra17. Ours is a tertiary institute with maximum referral of all dengue patients in district. Common man and even general practioners have misconception about the management and outcome of disease. There is lack knowledge about protocols about treatment of dengue and its complications. Many lives can be saved by just spreading the knowledge about the correct management protocols.

 

MATERIALS AND METHODS

It was a retrospective study included sixty eight patients with serologically confirmed dengue infection who required hospital admission in Bharati Vidyapeeth Deemed University Medical College and Hospital, Sangli during the study period. Study period 1 Jan 2012 to 31 Dec 2012.Patients was selected on basis of inclusion and exclusion criteria in study period. Data collected included the demographic details, details of clinical examination, and various laboratory parameters of blood counts, coagulation profile and biochemical investigation such as renal and hepatic function tests, treatment given, platelet transfusion and outcome of patient. Statistical analysis of data was done. The Chi Square test was used for analysis of the variables. A value of P < 0.05 was considered significant.

 

OBSERVATION AND RESULTS

There are several markers to estimate age in the young skeleton.15 These are primarily based on structural and morphological changes with age and development. The appearance of centers of ossification is based on strict chronological sequence. They also fuse with the respective diaphyses following a time schedule. Age can be estimated from those changes in skeletal remains. Morphometry of several bones like clavicle can also be used as a marker of age. Also some bones like the symphysis pubis, undergoes a series of morphological changes with age. The cranial suture closure has been used to determine the age in the mid adult phase and older group. Determination of age becomes less accurate with ageing.

 

Figure 1: Age and sex wise distribution of Patients

 

No specific age predilection for the disease.

Study Ratio

Lucknow

1.9:1

Singapore

1:0.57

Delhi

2.5:1

Present Study

1.4:1

 

The lower incidence in women could probably be a statistical artifact due to the fact that women are less likely to be taken for care at hospital and lower reporting from traditional practitioners who do not report to public surveillance systems.

Figure 2: Clinical features of patients with dengue

Fever Myalgia and petechiae were most common presentations of patients under study.

 

Figure 3: Bleeding Manifestations Seen in Patients Under Study

Petechiae was the most common bleeding manifestation seen in patients under study

 

Figure 4: Platelet count in patients with severe hemorrhage

 

Study Finding

 Lye et al : Degree of thrombocytopenia did not correlate with bleeding risk.

Present STD: Degree of thrombocytopenia did not correlate with bleeding risk.

 

Figure 5: Comparison of bleeding manifestation with presence of shock

Shock was seen in 24 patients (35.29%) of the patients, 11 (16.17%) had compensated shock (systolic blood pressure maintain but signs of reduced perfusion present) and 13 (19.11%) presents with hypotensive shock (systolic BP < 90 mmHg) Eleven patients with shock succumbed to the disease. Among the 11 patients with compensated shock, there were 4 deaths and 7 patients recovered. In those with hypotensive shock, there were 7 deaths and 6 patients improved.

 

Figure 4: Comparison of mortality with shock

 

Twenty four patients in this study developed shock. Among these patients thirteen improved while eleven patients had a fatal outcome. Analysis of the above data using the Chi-square test (P value of 0.000) revealed a significant association of shock with mortality.

 

Figure 5: Outcome in patients who received platelet transfusion and those that did not

 

A p value of 0.187 was obtained using the Chi square test which was not statistically significant.

Study Finding

Lye et al: efficacy of prophylactic platelet transfusion is questionable.

Lum et al: in DSS prophylactic transfusion of platelets and FFPs did not reduce bleeding or expedite platelet recovery,

Present Std- There was no difference seen in the overall outcome in patients who were transfused with platelets and those who did not receive any platelet transfusion.

 

CONCLUSION

For effective management of an acute and potentially fatal illness like dengue a standard protocol should be followed for prompt diagnosis and effective treatment to decrease mortality. The main factor contributing to the mortality was the presence of shock which lead to severe hemorrhage and organ dysfunction. The main focus in the management of dengue should be on preventing the development of shock and rapid correction of shock with careful i.v. fluid administration. The key is to maintain the blood pressure to prevent tissue hypoxia and organ dysfunction. Platelet count does not correlate with severity of hemorrhage or mortality. The role of platelet transfusion is controversial. From this study we can conclude that though prophylactic transfusions are unnecessary, platelet transfusions may be of benefit in patients with thrombocytopenia and hemorrhage, which continues despite blood transfusion.

 

LIMITATIONS

Though the analysis of the overall outcome in patients who received platelet transfusions and those who did not receive platelets did not show a significant difference in this study. A larger number of patients would have to be studied to see how the transfusion of blood products such as platelets and fresh frozen plasma influence the outcome of the disease, or whether they are really unnecessary. We could not compare the effectiveness of various IV fluids (crystalloids v/s colloids) used for initial resuscitation

 

DISCUSSION

Dengue infection has a wide clinical spectrum which includes both severe and non severe clinical manifestations. For a disease so complex in its manifestations, the management is relatively simple and inexpensive. Fluid resuscitation is usually the sole intervention required. However triage and management decisions at primary and secondary care levels are critical in determining the clinical outcome. In the present study 68 patients of dengue infection requiring hospital admission due to hypotension, bleeding manifestations, evidence of fluid leak, organ impairment, pregnancy, or other co morbid conditions were included. The study included 68 patients with forty (58.82%) male and twenty eight (41.17%) female patients. The ages of the patients ranged from 12 to 75 years. Forty three patients (63.23%) were in the age group of 21 to 40 years, with 30 males (44.11%) and 13 females (19.11%) in this age group. Dengue fever was typically thought to be a childhood disease, but now there is evidence of increasing incidence of dengue hemorrhagic fever among older age groups. Several studies in Southeast Asia and Latin America have reported a higher association of DHF with older ages. Surveillance data also showed a shift in peak dengue mortality from pediatric ages to adults. This shift in the modal age of illness will have a greater impact on the earning capacity and productivity of the community and greater economic loss.(6) Majority of the patients (64.2%) in this study were in the economically productive age group of 21-40 years, contributing significantly to the economic burden of the disease. In this study the male to female ratio of patients was 1.4:1. Three independent studies from epidemics in India and Singapore found twice the number of males as compared to females (Lucknow7 and8 Singapore both reported a male to female ratio of 1.9:1 and Delhi 1:0.57). In a hospital based study in Delhi during the 1996 epidemic, Wali9 reported an even higher ratio of 2.5:1. The lower incidence in women could probably be a statistical artifact due to lower reporting and care seeking from traditional practitioners who do not report to public surveillance systems. In many communities it is often seen that women are less likely to be taken for care at a hospital or are taken at late stages, when no other options are available. This could also lead to lower reporting of the disease in women.6The most common clinical features were fever (100%), athralgia and myalgia (98.53%), rash (86.76%), petechiae (92.65%), bleeding manifestations (75%). Hemorrhagic manifestations were seen in fifty three patients, of which twenty patients had major bleeding manifestations (hematemesis, malena, bleeding per rectum, hemoperitoneum) and the rest had minor bleeding manifestations (ecchymosis, purpura, subconjunctival hemorrhage). Twelve patients had only petechiae but no other bleeding manifestations. Hemorrhage is one of the major manifestations of DHF/DSS. Although severe bleeding occurs in DHF/DSS, it is multifactorial and not caused by thrombocytopenia alone. Lum et al in their study identified duration of shock and a low-normal hematocrit at the diagnosis of shock, as the strongest risk factors for hemorrhage. This suggests that patients with prolonged shock not only had plasma leakage but also bleeding causing the hematocrit to decrease. Prolonged prothrombin time and partial thromboplastin time were not directly responsible for severe bleeding; they were more likely to be prolonged in protracted shock. When major bleeding occurs, it is almost always associated with profound shock; this in combination with thrombocytopenia, hypoxia, and metabolic acidosis leads to progressive organ failure and advanced DIC. Massive bleeding can also occur in the absence of prolonged shock when aspirin, NSAIDs or corticosteroids have been taken.10

A similar association was seen in this study. Twenty patients in the study group had severe hemorrhage. In sixty percent of these patients severe hemorrhage was associated with shock (40% had severe bleeding in the absence of shock). On statistical analysis of data it was seen that there was a significant association between shock and the presence of severe bleeding (p value =0.004) in the patients studied. This correlates with the findings of previous studies which indicate the presence of shock as a major determinant for the development of bleeding. Shock occurs when a critical volume of plasma is lost through leakage. The onset of shock is usually preceded by warning signs. During the initial stages of shock, compensatory mechanisms maintain a normal systolic blood pressure, producing tachycardia and peripheral vasoconstriction (compensated shock).10 There is rise of diastolic blood pressure towards systolic blood pressure leading to a narrow pulse pressure. Finally there is decompensation and both pressures disappear (hypotensive shock). Twenty four (34.2%) patients in the study group presented with shock. Eleven patients had compensated shock (maintained systolic BP with signs of reduced perfusion) and thirteen had hypotensive shock. The mortality among the patients with shock was 45.8% i.e. eleven patients with shock succumbed to the disease. However there was no predilection for the development of shock seen in any particular age group. Thrombocytopenia is the most common hematological finding in patients with dengue infection. Thrombocytopenia is caused due to IgM antiplatelet antibodies which induce platelet lysis via complement activation11. 50 patients in this study had a platelet count of less than 50,000/uL at presentation. The mean platelet count at admission was 46,085/uL. None of the patients with severe hemorrhage had platelet counts <20,000/uL; 16 patients with severe bleeding had counts between 20,000-49,000/uL and four of these patients had a platelet count of> 50,000/uL. This shows that the platelet count does not correlate with the severity of bleeding. The latest WHO guidelines12 emphasize that judicious intravenous fluid resuscitation is essential and usually the sole intervention required. This strategy is different from simple fluid administration. Here larger volumes of fluid boluses are administered for a limited period of time under close monitoring to evaluate the patient s response and avoid the development of pulmonary edema. The guidelines state that there is no clear advantage of colloid over crystalloid fluids in terms of overall outcome. However, colloids may be the preferred choice if blood pressure has to be restored urgently (<10 mm of Hg) 10. Premratna et al4 suggest that during the resuscitation of patients who already have evidence of third space fluid accumulation at the time of developing DSS, use of colloids rather than crystalloids would prevent the development of recovery phase pulmonary edema Wills et al44 in their double blind randomized comparison of fluid for initial resuscitation of children with DSS concluded that resuscitation with crystalloids was acceptable for children with moderately severe DSS, there was no clear benefit with the use of colloid solutions in these children. However their study did not address the use of crystalloids in profound or recurrent shock, in which colloid solutions are thought to be beneficial despite a lack of good supporting evidence. In this study group all patients received crystalloid solution for fluid resuscitation. Patients with profound shock and coagulopathy received fresh frozen plasma and blood. The assessment of the efficacy of colloid solutions versus crystalloids in the resuscitation of patients with shock was limited by the unavailability of colloid solutions such as dextrans, starch, gelatin etc. For the treatment of hemorrhage, WHO recommends blood transfusion as soon as severe bleeding is suspected or recognized There is emphasis for the use of fresh whole blood for optimal oxygen delivery to tissues (stored blood loses 2, 3-DPG leading to decreased oxygen releasing capacity of hemoglobin)(10). Nineteen patients received whole blood and twelve received packed cells. These were the patients who had shock and severe bleeding manifestations. Though there is emphasis on use of fresh whole blood, increased demand for blood in our hospital leads to unavailability of fresh blood. Therefore, some patients received stored whole blood and packed cells for the treatment of hemorrhage. The role of platelet transfusion in DHF/DSS remained controversial. Multiple studies have shown no benefit of prophylactic platelet transfusion in outcome of the disease. It has also been noted that the platelet count is not predictive of bleeding. Lye et al (13) in their study observed that thrombocytopenia did not correlate with bleeding risk and the efficacy of prophylactic platelet transfusion is questionable. Lum et al (14) noted that in pediatrics DSS prophylactic transfusion of platelets and FFPs did not reduce bleeding or expedite platelet recovery, instead it caused fluid overload and prolonged hospitalization, and the improvement in platelet count was transient less than five hours. The WHO guidelines state that "prophylactic platelet transfusion for severe thrombocytopenia in otherwise hemodynamically stable patients have not been shown to be effective and are not necessary"10. In patients with hemorrhage, "there is little evidence to support the practice of transfusing the platelets and FFPs for severe bleeding. It is being practiced massive bleeding cannot be managed with just fresh whole blood or packed cells, but it may exacerbate fluid overload "10 Other guidelines (18) say that although prophylactic transfusions are not recommended, they may be "required in a patient with thrombocytopenia who is to undergo an urgent surgery, has active bleeding which continues inspite of repeated blood transfusions, DIC or in patients with intracranial hemorrhage." Ahluwalia et al19 suggest that "since there is no other specific therapy for DHF/DSS, patients with bleeding tendency and/or a platelet count less than 25000 may be transfused platelets." Twenty eight patients in this study received platelet transfusion, of these 12 patients had severe bleeding manifestations. Platelet transfusions were given to patients with clinical bleeding with thrombocytopenia. No prophylactic platelet transfusions were given In the group of patients received platelet transfusion there were 7 deaths and 21 patients improved. On statistical analysis there was no significant difference in outcome, seen in those who received and those who did not receive platelets (p=0.l29). Since the number of patients who received transfusion was small (30 patients), it is difficult to comment whether platelet transfusion actually decreased mortality. However, since no adverse outcome was seen in patients who received platelet transfusion, it may suggest that platelet transfusion in those with active bleeding (persisting despite blood transfusion) and low platelet counts may be of some benefit. Further evaluation needs to be done. There was a mortality of 15.7% in the patients studied. Eleven of seventy patients succumbed to the disease, of these there were ten male and only one female death. There was no specific association of mortality with any particular age group in the study population. All the eleven patients who died were in shock at the time of presentation, seven (63.6%) of these had hypotensive shock and four (36.3%) patients had compensated shock. There was statistically significant association of shock with mortality (p value = 0.000). This shows that prolonged shock is a major factor contributing to death as it leads to hypoxia, organ dysfunction, DIC and severe hemorrhage. Seven (63.6 %) patients who succumbed to dengue had severe bleeding manifestations (hematemesis, massive bleeding PR, hemoperitoneum), two patients had minor bleeding (subconjunctival hemorrhage, oral bleeding), two patients only had petechiae with no other bleeding manifestation. The platelet count did not correlate with the severity of bleeding or mortality. Only one patient who died had a platelet count <20,000/uL at admission, seven patients had platelet count in the range 20,000 to 49,000/uL and three patients had platelet count of >50,000/uL at admission.

 

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