SARI PUSTAKA Kepada Yth. dr. Handre Putra Bapak/Ibu …………………… Senin, 28 Desember 2015 SKORING INFEKSI DENGUE SEBAGAI PREDIKTOR DERAJAT KEPARAHAN INFEKSI DENGUE Oleh: dr. Handre Putra Pembimbing: dr. Rinang Mariko, Sp.A(K) BAGIAN ILMU KESEHATAN ANAK FAKULTAS KEDOKTERAN UNIVERSITAS ANDALAS/ RSUP DR. M. DJAMIL PADANG 2015
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Skoring Infeksi Dengue Sebagai Prediktor Derajat Keparahan Infeksi Dengue
Skoring Infeksi Dengue sebagai Prediktor Derajat Keparahan Infeksi Dengue
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SARI PUSTAKA Kepada Yth.
dr. Handre Putra Bapak/Ibu ……………………Senin, 28 Desember 2015
SKORING INFEKSI DENGUE SEBAGAI PREDIKTOR DERAJATKEPARAHAN INFEKSI DENGUE
Oleh:dr. Handre Putra
Pembimbing:dr. Rinang Mariko, Sp.A(K)
BAGIAN ILMU KESEHATAN ANAKFAKULTAS KEDOKTERAN UNIVERSITAS ANDALAS/
RSUP DR. M. DJAMIL PADANG2015
i
KATA PENGANTAR
Puji syukur penulis ucapkan kehadirat Allah SWT karena berkat
karuniaNya sari pustaka yang berjudul “Skoring Infeksi Dengue Sebagai Prediktor
Derajat Keparahan Infeksi Dengue” dapat penulis selesaikan.
Penulis mengucapkan terima kasih kepada dr. Rinang Mariko, Sp.A(K)
sebagai pembimbing yang telah meluangkan waktu dan memberikan banyak
masukan dalam penyusunan sari pustaka ini. Terima kasih juga kepada guru-guru,
para senior, dan rekan-rekan sejawat yang ikut membantu sampai selesainya sari
pustaka ini.
Penulis menyadari bahwa sari pustaka ini masih memiliki banyak
kekurangan, dan ilmu yang diangkat pada sari pustaka ini merupakan ilmu yang
senantiasa berubah dan berkembang. Untuk itu penulis sangat mengharapkan
kritik dan saran untuk perbaikan. Semoga sari pustaka ini dapat memberi manfaat
dan menambah khazanah ilmu pengetahuan.
Padang, 19 Desember 2015
Penulis
ii
DAFTAR ISI
KATA PENGANTAR.................................................................................................. i
DAFTAR ISI ............................................................................................................. ii
DAFTAR GAMBAR ................................................................................................ iii
DAFTAR TABEL ..................................................................................................... iv
DAFTAR SINGKATAN............................................................................................. v
BAB I PENDAHULUAN .......................................................................................... 1
BAB II INFEKSI VIRUS DENGUE ........................................................................... 3
Sistem skoring oleh Pongpan dkk memprediksi DSS dengan benar, nilai
positive predictive value (PPV) yaitu 88% dan hasil ini sama dengan PPV dari
skor PELOD, PRISM III dan analisis CART, yaitu 82-95%.7 Sistem skoring ini
sudah dilakukan validasi pada tahun 2014 dengan hasil kurang akurat pada data
validasi, hal ini mungkin disebabkan pasien pada data validasi lebih atau kurang
derajat keparahannya daripada pasien dari data sebelumnya. Akan tetapi dari
perspektif klinis skoring ini sangat berguna bila diaplikasikan dalam praktek klinis
sehari-hari, karena hanya membutuhkan data klinis sederhana yang biasa
diperiksa secara rutin. 58
28
KESIMPULAN
Infeksi dengue disebabkan oleh virus dengue yang terdiri atas empat serotipe yaitu
DEN-1, DEN-2, DEN-3 dan DEN-4 yang ditularkan melalui gigitan nyamuk
Aedes aegypti dan Aedes albopictus. Infeksi oleh salah satu dari empat serotipe di
atas akan menyebabkan spektrum klinis yang berbeda. Kebocoran plasma
merupakan faktor utama yang membedakan tingkat keparahan penyakit akibat
infeksi virus dengue.
Pada awal infeksi sangat sulit membedakan infeksi dengue ringan dengan
kasus berat, sehingga sering terjadi underdiagnosis maupun overdiagnosis infeksi
dengue. Untuk itu diperlukan alat prognostik sederhana seperti sistem skoring
yang diperoleh berdasarkan faktor risiko klinis dan laboratorium sederhana yang
telah diteliti memiliki peranan dalam menentukan derajat keparahan infeksi
dengue. Skoring infeksi dengue yang dikembangkan Pongpan dkk tahun 2013
menggunakan parameter klinis dan pemeriksaan labor rutin sederhana untuk
menentukan derajat keparahan infeksi dengue. Parameter yang digunakan antara
lain usia, hepatomegali, hematokrit, tekanan darah sistolik, leukosit dan trombosit.
Parameter ini sangat sederhana dan mudah digunakan pada layanan kesehatan
primer dengan fasilitas terbatas. Sehingga dapat diaplikasikan dalam praktek
klinis sehari-hari dan dapat membantu untuk mengurangi rawatan yang tidak
diperlukan karena overdiagnosis serta mengurangi mortalitas akibat
underdiagnosis.
29
DAFTAR PUSTAKA
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2. Srikiatkhatchorn A, Green S. Markers of dengue disease severity. Currenttopic in microbiology and Immunology. 2010;338:67-79
3. Leong AS, Wong KT, Leong TY, Tan PH, Wannakrairot P. The pathologyof dengue hemorrhagic fever. Seminars in Diagnostic Pathology.2007;24:227-36
4. World Health Organization. Dengue guidelines for diagnosis, treatment,prevention and control new edition. Geneva. WHO. 2009
5. Aditama TY. Demam berdarah biasanya mulai meningkat di Januari.Diunduh dari http://www.depkes.go.id. Diunduh pada tanggal 29 November2015
6. Megariani, Mariko R, Alkamar A, Putra AE. Uji diagnostik pemeriksaanantigen nonstruktural 1 untuk deteksi dini infeksi virus dengue pada anak.Sari Pediatri. 2014;16(2):121-7
7. Pongpan S, Wisitwong A, Tawichasri C, Patumanond J, Namwongprom S.Clinical study development of dengue infection severity score. HindawiPublishing Corporation ISRN Pediatrics. 2013;6:1-6
8. Potts JA, Gibbons RV, Rothman AL, Srikiatkachorn A, Thomas SJ,Supradish PO, dkk. Prediction of dengue disease severity among pediatricThai patients using early clinical laboratory indicators. PLoS NeglectedTropical Diseases. 2010;4(8):1-7
10. Karyanti MR, Uiterwaal CSPM, Kusriastuti R, Hadinegoro SR, RoversMM, Heesterbeek H, et all. The changing incidence of dengue haemorrgahicfever in Indonesia: a 45-year registry-base analysis. BMC Infectiousdisease. 2014;14:1-7
11. Fahri S, Yohan B, Trimarsanto H, Sayono S, Hadisaputro S, Dharmana E, etall. Molecular surveillance of dengue in Semarang, Indonesia revealed thecirculation of an old genotype of dengue virus serotype-1. PLOS.2013;7(8):1-12
12. Sasmono RT, Wahid I, Trimarsanto H, Yohan B, Wahyunu S, Hertanto M,et all. Genomic analysis and growth characteristic of dengue viruses fromMakassar, Indonesia. Infection, Genetics and Evolution-Elsevier.2015;32:165-77
13. Gubler DJ, John AS. Dengue Viruses. Elsevier. 2014:1-1414. Guzman MG, Vazquez S. The complexity of antibody dependent
enhanchement of dengue virus infection. Viruses. 2010;2:2649-6215. Kurane I. Dengue hemorrhagic fever with special emphasis on
immunopathogenesis. Microbiol Infect Dis. 2006;30:329-4016. Hadinegoro SR, Moedjito I, Chairulfatah A. Patogenesis Infeksi Dengue
dalam Pedoman Diagnosis dan Tatalaksana Infeksi Virus Dengue padaAnak Edisi 1. Badan Penerbit Ikatan Dokter Anak Indonesia. 2014;(1):7-12
30
17. Soegijanto S. Patogenesa infeksi virus dengue recent update. Managementof Dengue Viral Infection in Children. 2010;10:11-45
18. John ALS, Abraham SN, Gubler D. Barriers to preclinical investigations ofanti-dengue immunity and dengue pathogenesis J. Nature MacmilanPublisher. 2013;11:420-6
19. World Health Organization-South East Asia Regional Office.Comprehensive Guidelines for Prevention and Control of Dengue andDengue Hemorrhagic Fever. India: WHO; 2011
20. Wright WF, Pritt BS. Update: the diagnosis and managementof denguevirus infection in North American.Diagnostic Microbiology and InfectiousDisease. 2012;73:215-20
22. Darwish NT, Alias YB, Khor SM. An introduction to dengue-diseasediagnostic. Trends in Analytical Chemistry. 2015;67:45-55
23. Amorim JH, Alves RDS, Boscardin SB, Ferreira LSDS. The dengue virusnon-structural 1 protein: risks and benefits. Virus Research. 2014;181:53-60
24. Dussart P, Labeau B, Lagathu G. Evaluation of an enzyme immunoassay fordetection of dengue virus NS1 antigen in human serum. Plos.2006;13:1185–9
25. Datta S, Wattal C. Dengue NS1 antigen detection: A useful tool in earlydiagnosis of dengue virus infection.Indian J Med Microbiol 2010;28:107-10
26. Kumarasamy V, Chua SK, Hassan Z, Wahab AH, Chem YK, Mohamad M,dkk. Evaluating the sensitivity of a commercial dengue NS1 antigen-captureElisa for early diagnosis of acute dengue infection. Singapore Med J2007;48:669-73
28. Pongpan S, Wisitwong A, Tawichasri C, Patumanond J. Prognosticindicators for dengue infection severity. Int K Clin Pediatr. 2013;2(1):12-8
29. Phubhakdi CB, Hemungkorn M, Thisyakorn U, Thisyakorn C. Risk factorsinfluencing severity in pediatric dengue infection. Asian Biomedicine.2008;2(5):409-13
30. Anders KL, Nguyet NM,Chau NVV, Hung NT, Thuy TT, Lien LB, et all.Epidemiological factors associated with dengue shock syndrome andmortality in hospitalized dengue patients in Ho Chi Minh city, Vietnam.2011;123-34
31. Anker M, Arima Y. Male-female differences in the number of reportedincident dengue fever cases in six Asian countries. Western PacificSurveillance and Response Journal. 2011;2(2):17-23
32. Hammond SN, Balmaseda A, Perez L, Tellez Y, Saborio SI, Mercado JC, etal. Differences in dengue severity in infants, children, and adults in a 3-yearhospital-based study in Nicaragua. Am J Trop Med Hyg. 2005;73(6):1063-70
33. Junia J, Garna H, Setiabudi D. Clinical risk factors for dengue shocksyndrome in children. Paediatr Indones. 2007;47(1):7-11
31
34. Pham Tb, Nguyen TH, Vu TQ, Nguyen TL, Malvy D. Predictive factors ofdengue shock syndrome at the children hospital No. 1, Ho-Chi-Minh City,Vietnam. 2007;100(1):43-7
35. Gupta V, Yadav TP, Pandey RM, Singh A, Gupta M, Kanaujiya P, et al.Risk factors of dengue shock syndrome. Journal of Tropical Pediatrics.2011;57:451-6
36. Petdachai W. Hepatic dysfunction in children with dengue shock syndrome.Dengue Bull 2005;29:112-7
37. Falconar AKI, Romero-vivas CME. Simple prognostic criteria candefinitely identify patients who develop severe versus non-severe denguedisease, or have other febrile illnesses. J Clin Med Res. 2011;4(1):33-44
38. Roy A, Sarkar D, Chakraborty S, Chaudhuri J, Ghosh P, Chakraborty S.Profile of hepatic involvement by dengue virus in dengue infected children.2013. North American Journal of Medical Sciences. 2013;5(8):480-5
39. Ledika Ma, Setiabudi D, Dhamayanti M. Association between clinicalprofiles and severe dengue infection in children in developing country.American Journal of Epidemiology and Infectious Disease. 2015;3(3):45-9
40. Kittigul L, Pitakarnjanakul P, Sujirarat D, Siripanichgon K. The differencesof clinical manifestations and laboratory findings in children and adults withdengue virus infection. J Clin Virol. 2007;39(2):76-81.
41. Weerakoon KGAD, Chandrasekaram S, Jayabahu JPSNK, Gunasena S,Kularatne SAM. Acute abdominal pain in dengue haemorrhagic fever: Astudy in Sri Lanka. Dengue Bulletin. 2009;33:70-4
42. Khanna S, Vij JC, Kumar A, Singal D, Tandon R. Etiology of AbdominalPain in Dengue Fever. Dengue Bulletin. 2005;29:85-9
43. Srikiatkachorn A, Krautrachue A, Ratanaprakarn W, Wongtapradit L,Nithipaya N, Kalayanarooj S, et al. Natural history of plasma leakage indengue hemorrhagic fever: a serial ultrasonographic study. PediatricInfectious Disease Journal. 2007;26(4):283-90
44. Hawarini N, Kosim MS, Supriatna M, Istanti Y, Sudjianto E. Therelationship between pleural effusion index and mortality in children withdengue shock syndrome. 2012;52(4):239-42
45. Ejaz K, Khursheed M, Raza A. Pleural effusion in dengue. 2011;32(1):46-946. Espinosa JN, Dantes HG, Quintal JGC, Martinez JLV. Clinical profile of
dengue hemorrhagic fever cases in Mexico. Salud Publica de Mexico 2005;47:193-200
47. Lam PK, Tam DTH, Dung NM, Tien NTH, Kleu NTT, Simmons C, et al. APrognostic Model for Development of Profound Shock among ChildrenPresenting with Dengue Shock Syndrome. PLOS one. 2015;10(5):1-13
48. Balasubramania S, Anandnathan K, Shivabalan SO, Data M, Amalraj E.Cut-off hematocrit value for hemoconcentration in dengue hemorrhagicfever. Journal pf Tropical Pediatrics Oxford University Press.2005;50(2):123-4
49. Singhi S, KissoonN, Bansal A. Dengue and dengue hemorrhagic fever:management issues in an intensive care unit. J Pediatr (Rio J).2007;83(2Suppl):S22-35
50. Mayetti. Hubungan klinis dan laboratorium sebagai faktor risiko syok padaDBD. Sari Pediatri. 2010;11(5):367-72
32
51. Azeredo ELD, Monteiro RQ, Pinto LMDO. Thrombocytopenia in dengue:interrelationship between virus and the imbalance between coagulation andfibrinolysis and inflammatory mediators. Hindawi Publishing CorporationMediators of Inflammation. 2015;10:1-17
52. Narayanan M, Aravind MA, Ambikapathy P. Dengue fever-clinical andlaboratory parameters associated with complications. Dengue Bulletin 2003;27:108-15
53. Wichmann O, Hongsiriwon S, Bowonwatanuwong C, Chotivanich K,Sukhtana Y, Pukrittayakamee. Risk factors and clinical features associatedwith severe dengue infection in adults and children during the 2001epidemic in Chonburi, Thailand. Trop Med and Int Health 2004;9:1022-9
54. Dewi R, Tumbelaka AR, Sjarif DR. Clinical features of dengue hemorrhagicfever and risk factors of shock event. Pediatr Indones. 2006;46:144-8
55. Samanta J, Sharma V. Dengue and its effect on liver. World J Clin Cases.2015;3(2):125–31
56. Shah I, Deshpande GC, Tardeja PN. Outbreak of dengue in Mumbai andpredictive markers for dengue shock syndrome. J Trop Pediatr.2004;50(5):301-305
57. Tanner L, Schreiber M, Low JGH, Ong A, Tolfvenstam T, Lai YL, et al.Decision tree algorithms predict the diagnosis and outcome of dengue feverin the early phase of illness. Plos Negl Trop Dis. 2008;2;1-8
58. Pongpan S, Patumanond J, Wisitwong A, Tawichasri C, Namwongprom S.Validation of dengue infection severity score. Dovepress. 2014;3:45-9
33
1 Candra A. Demam berdarah dengue: epidemiologi, pathogenesis, dan faktor risiko penularan.Aspirator. 2010;2:110-92 Srikiatkhatchorn A, Green S. Markers of dengue disease severity. Current topic in
microbiology and Immunology. 2010;338:67-793 Leong AS, Wong KT, Leong TY, Tan PH, Wannakrairot P. The pathology of dengue hemorrhagicfever. Seminars in Diagnostic Pathology. 2007;24:227-364 World Health Organization. Dengue guidelines for diagnosis, treatment,
prevention and control new edition. 2009. Geneva.5 Aditama TY. Demam berdarah biasanya mulai meningkat di Januari. Diunduh darihttp://www.depkes.go.id. Diunduh pada tanggal 29 November 20156 Megariani, Mariko R, Alkamar A, Putra AE. Uji diagnostik pemeriksaan antigen nonstruktural 1untuk deteksi dini infeksi virus dengue pada anak. Sari Pediatri. 2014;16(2):121-77 Potts JA, Gibbons RV, Rothman AL, Srikiatkachorn A, Thomas SJ, Supradish PO, dkk. Prediction ofdengue disease severity among pediatric Thai patients using early clinical laboratory indicators.PLoS Neglected Tropical Diseases. 2010;4(8):1-7
8 Pongpan S, Wisitwong A, Tawichasri C, Patumanond J, Namwongprom S. Clinical studydevelopment of dengue infection severity score. Hindawi Publishing Corporation ISRN Pediatrics.2013;6:1-69 Soedarmo SSP, Garna H, Hadinegoro SRS, Satari HI. Infeksi Virus Dengue dalam Buku Ajar Infeksi& Pediatri Tropis. 2008. IDAI;2:155-8110 Karyanti MR, Uiterwaal CSPM, Kusriastuti R, Hadinegoro SR, Rovers MM, Heesterbeek H, et all.The changing incidence of dengue haemorrgahic fever in Indonesia: a 45-year registry-baseanalysis. BMC Infectious disease. 2014;14:1-711 Fahri S, Yohan B, Trimarsanto H, Sayono S, Hadisaputro S, Dharmana E, et all. Molecularsurveillance of dengue in SemarangIndonesia revealed the circulation of an old genotype ofdengue virus serotype-1. PLOS. 2013;7(8):1-1212 Sasmono RT, Wahid I, Trimarsanto H, Yohan B, Wahyunu S, Hertanto M, et all. Genomicanalysis and growth characteristic of dengue viruses from Makassar, Indonesia. Infection,Genetics and Evolution-Elsevier. 2015;32:165-7713 Gubler DJ, John AS. Dengue Viruses. Elsevier. 2014:1-1414 Guzman MG, Vazquez S. The complexity of antibody dependent enhanchement of dengue virusinfection. Viruses. 2010;2:2649-62.15 Kurane I. Dengue hemorrhagic fever with special emphasis on immunopathogenesis. MicrobiolInfect Dis. 2006;30:329-40.
34
16 Hadinegoro SR, Moedjito I, Chairulfatah A. Patogenesis Infeksi Dengue dalam PedomanDiagnosis dan Tatalaksana Infeksi Virus Dengue pada Anak Edisi 1. Badan Penerbit Ikatan DokterAnak Indonesia. 2014;(1):7-1217 Soegijanto S. Patogenesa infeksi virus dengue recent update. Management of
Dengue Viral Infection in Children. 2010;10:11-45.
18 John ALS, Abraham SN, Gubler D. Barriers to preclinical investigations of anti-dengue immunityand dengue pathogenesis J. Nature Macmilan Publisher. 2013;11:420-619 World Health Organization-South East Asia Regional Office. Comprehensive Guidelines forPrevention and Control of Dengue and Dengue Hemorrhagic Fever. India: WHO; 2011.20 Wright WF, Pritt BS. Update: the diagnosis and managementof dengue virus infection in NorthAmerican.Diagnostic Microbiology and Infectious Disease. 2012;73:215-2021 Peeling RW, Artsob H, Pelegrino JL, Buchy P, Cardosa MJ, Devi S, et al. Evaluation of diagnostictests: dengue. 2010;8(12 Suppl):30-8.22 Darwish NT, Alias YB, Khor SM. An introduction to dengue-disease diagnostic. Trends inAnalytical Chemistry. 2015;67:45-5523 Amorim JH, Alves RDS, Boscardin SB, Ferreira LSDS. The dengue virus non-structural 1 protein:risks and benefits. Virus Research. 2014;181:53-6024 Dussart P, Labeau B, Lagathu G. Evaluation of an enzyme immunoassay for detection of denguevirus NS1 antigen in human serum. Plos. 2006;13:1185–9.25 Datta S, Wattal C. Dengue NS1 antigen detection: A useful tool in early diagnosis of denguevirus infection.Indian J Med Microbiol 2010;28:107-10.26 Kumarasamy V, Chua SK, Hassan Z, Wahab AH, Chem YK, Mohamad M, dkk. Evaluating thesensitivity of a commercial dengue NS1 antigen-capture Elisa for early diagnosis of acute dengueinfection. Singapore Med J 2007;48:669-73.27 Garcia CJA, Guzman GFJ, Alejandro QVM, Ruiz MCG, Sachez HM, Lemarroy CRC. Denguehemorrhagic fever in infant after primoinfection.Bol Med Hosp Infant Mex. 2010;67:355-8.28 Phubhakdi CB, Hemungkorn M, Thisyakorn U, Thisyakorn C. Risk factors influencing severity inpediatric dengue infection. Asian Biomedicine. 2008;2(5):409-1329 Anders KL, Nguyet NM,Chau NVV, Hung NT, Thuy TT, Lien LB, et all. Epidemiological factorsassociated with dengue shock syndrome and mortality in hospitalized dengue patients in Ho ChiMinh city, Vietnam. 2011;123-3430 Anker M, Arima Y. Male-female differences in the number of reported incident dengue fevercases in six Asian countries. Western Pacific Surveillance and Response Journal. 2011;2(2):17-2331 Hammond SN, Balmaseda A, Perez L, Tellez Y, Saborio SI, Mercado JC, et al. Differences indengue severity in infants, children, and adults in a 3-year hospital-based study in Nicaragua. AmJ Trop Med Hyg. 2005;73(6):1063-7032 Junia J, Garna H, Setiabudi D. Clinical risk factors for dengue shock syndrome in children.Paediatr Indones. 2007;47(1):7-11.33 Pham Tb, Nguyen TH, Vu TQ, Nguyen TL, Malvy D. Predictive factors of dengue shock syndromeat the children hospital No. 1, Ho-Chi-Minh City, Vietnam. 2007;100(1):43-734 Gupta V, Yadav TP, Pandey RM, Singh A, Gupta M, Kanaujiya P, et al. Risk factors of dengueshock syndrome. Journal of Tropical Pediatrics. 2011;57:451-635 Petdachai W. Hepatic dysfunction in children with dengue shock syndrome. Dengue Bull2005;29:112-736 Falconar AKI, Romero-vivas CME. Simple prognostic criteria can definitely identify patients whodevelop severe versus non-severe dengue disease, or have other febrile illnesses. J Clin Med Res.2011;4(1):33-4437 Roy A, Sarkar D, Chakraborty S, Chaudhuri J, Ghosh P, Chakraborty S. Profile of hepaticinvolvement by dengue virus in dengue infected children. 2013. North American Journal ofMedical Sciences. 2013;5(8):480-5
35
38 Ledika Ma, Setiabudi D, Dhamayanti M. Association between clinical profiles and severedengue infection in children in developing country. American Journal of Epidemiology andInfectious Disease. 2015;3(3):45-939 Kittigul L, Pitakarnjanakul P, Sujirarat D, Siripanichgon K. The differences of clinicalmanifestations and laboratory findings in children and adults with dengue virus infection. J ClinVirol. 2007;39(2):76-81.40 Weerakoon KGAD, Chandrasekaram S, Jayabahu JPSNK, Gunasena S, Kularatne SAM. Acuteabdominal pain in dengue haemorrhagic fever: A study in Sri Lanka. Dengue Bulletin. 2009;33:70-441 Khanna S, Vij JC, Kumar A, Singal D, Tandon R. Etiology of Abdominal Pain in Dengue Fever.Dengue Bulletin. 2005;29:85-942 Srikiatkachorn A, Krautrachue A, Ratanaprakarn W, Wongtapradit L, Nithipaya N, KalayanaroojS, et al. Natural history of plasma leakage in dengue hemorrhagic fever: a serial ultrasonographicstudy. Pediatric Infectious Disease Journal. 2007;26(4):283-9043 Hawarini N, Kosim MS, Supriatna M, Istanti Y, Sudjianto E. The relationship between pleuraleffusion index and mortality in children with dengue shock syndrome. 2012;52(4):239-4244 Ejaz K, Khursheed M, Raza A. Pleural effusion in dengue. 2011;32(1):46-945 Espinosa JN, Dantes HG, Quintal JGC, Martinez JLV. Clinical profile of dengue hemorrhagic fevercases in Mexico. Salud Publica de Mexico 2005; 47:193-200.46 Lam PK, Tam DTH, Dung NM, Tien NTH, Kleu NTT, Simmons C, et al. A Prognostic Model forDevelopment of Profound Shock among Children Presenting with Dengue Shock Syndrome. PLOSone. 2015;10(5):1-1347 Balasubramania S, Anandnathan K, Shivabalan SO, Data M, Amalraj E. Cut-off hematocrit valuefor hemoconcentration in dengue hemorrhagic fever. Journal pf Tropical Pediatrics OxfordUniversity Press. 2005;50(2):123-448 Singhi S, KissoonN, Bansal A. Dengue and dengue hemorrhagic fever: management issues in anintensive care unit. J Pediatr (Rio J).2007;83(2 Suppl):S22-35.49 Mayetti. Hubungan klinis dan laboratorium sebagai faktor risiko syok pada DBD. Sari Pediatri.2010;11(5):367-7250 Azeredo ELD, Monteiro RQ, Pinto LMDO. Thrombocytopenia in dengue: interrelationshipbetween virus and the imbalance between coagulation and fibrinolysis and inflammatorymediators. Hindawi Publishing Corporation Mediators of Inflammation. 2015;10:1-1751 Narayanan M, Aravind MA, Ambikapathy P. Dengue fever-clinical and laboratory parametersassociated with complications. Dengue Bulletin 2003; 27:108-15.52 Wichmann O, Hongsiriwon S, Bowonwatanuwong C, Chotivanich K, Sukhtana Y,Pukrittayakamee. Risk factors and clinical features associated with severe dengue infection inadults and children during the 2001 epidemic in Chonburi, Thailand. Trop Med and Int Health2004;9:1022-9.53 Dewi R, Tumbelaka AR, Sjarif DR. Clinical features of dengue hemorrhagic fever and risk factorsof shock event. Pediatr Indones. 2006;46:144-854 Samanta J, Sharma V. Dengue and its effect on liver. World J Clin Cases. 2015;3(2):125–31.55 Shah I, Deshpande GC, Tardeja PN. Outbreak of dengue in Mumbai and predictive markers fordengue shock syndrome. J Trop Pediatr. 2004;50(5):301-305.57 Pongpan S, Patumanond J, Wisitwong A, Tawichasri C, Namwongprom S. Validation of dengueinfection severity score. Dovepress. 2014;3:45-9