Blood is thicker than Water:

A case of Dengue Fever with Warning

Signs
Ivan Lendle Yenson MD
Post-Graduate Intern
 Objectives
• To present a pediatric case of dengue fever
• To discuss the basic pathophysiology, clinical features and management of dengue fever
• To present a journal relevant to the case presented
 K. A.
7 years old
Male
Filipino
Sought consult last
October 5, 2019 @
MDH-ER
Chief Complaint

Generalized Body
Weakness
 5

11 mkd
4
5
5 4

Rx CBC Parameters
Hemoglobin
Patient’s values
124
Normal Value
115-145 g/L
1. Co-Amoxiclav at 39.5 Hematocrit 40 33-43
mkday BID for 7 days RBC Count 4.80 4.00-5.30

2. Paracetamol Platelet 220 150-450

WBC Count 9.69 4.00-12.00
12mg/kg/dose prn for
Neutrophils 90
fever Lymphocytes 3
3. Betadine throat spray Monocytes 7
BID x 5 days
5 …
4
4 …
2
… 2
DOC
Review of Systems
Past Medical History
Immunization History
Family Medical History
 Personal and Social History

5 household members
Grade 2 student Paco, Manila
School in Pandacan (-) Similar illness
(+) Similar illness of fever (+) Dengue cases No travel history
(+) Dengue cases With good sanitation practices
Physical Examination
 Vital Signs
Awake
Blood Pressure: 100/60mmHg
Weak-looking
Heart rate: 122 bpm

Flushed36.7skin
Respiratory rate: 26 cpm
Temperature: o C
Height-for-Age
Weight-for-Age BMI-for-Age

Anthropometrics

Weight: 24.3 kgs

Height: 127cms
BMI: 15
IBW: 22kgs
 Head and Neck

(+) palatal petechiae

(-) tonsillopharyngeal congestion
 Chest and Lungs

(+) tachypneic
Clear breath sounds
 Heart

Tachycardic
Normal rhythm
(-) skipped beats
 Abdomen

(+) direct epigastric

tenderness
 Extremities

Full equal pulses

CRT < 2 seconds
 Salient Features

7 years old/ Male 2-day history of epigastric

Afebrile
pain
5 day-history of high grade
Generalized Body Weakness Tachycardic
fever
Colds Flushed Skin Tachypneic

(+) Throat pain Palatal Petechiae

Managed as ATP with Co-
Epigastric Tenderness
Amoxiclav
Approach to Diagnosis
 FOCUS?
Acute
Gastro-
Acute
enteritis Dengue
Tonsillo-
Fever
pharyngitis
One common side-effect of Co-
amoxiclav is GI disturbance
 Working Impression

Acute Tonsillopharyngitis, Resolving

r/o Dengue Fever
Course in the ER

CBC Parameters Patient’s values Normal Value

Hemoglobin 176 115-145 g/L

Hematocrit 51 33-43 Test Patient’s result

RBC Count 6.50 4.00-5.30 Dengue NS1 POSITIVE
Platelet 50 150-450
Dengue IgM POSITIVE
WBC Count 5.67 4.00-12.00
Dengue IgG POSITIVE
Neutrophils 58
Lymphocytes 31
Monocytes 11
 Working Impression

Dengue Fever with Warning Signs, Critical Phase

(Day 5 of illness, Day 0 afebrile)
Course in the Wards
October 05, 2019 (0 HD) Day 5 of Illness, Day 0 afebrile
Subjective Objective Plan
CBC Parameters Patient’s values Normal Value
BP: 90/60 mmHg Diet for age; Avoid dark-colored foods
Hemoglobin 162 115-145 g/L
HR: 122 bpm
RR: 26 cpm
Hematocrit 46 33-43
T: 36.7C
IVF: PLR 1L x 122 cc/hr for 2 hrs (5cc/kg/hr) then 97
RBC Count 5.99 4.00-5.30
(+) flushed skin cc/hr (3 cc/kg/hr)
(-) febrile episodes Platelet 34 150-450
(+) epigastric for 4 hours
(-) bleeding WBC Count
tenderness 6.98 4.00-12.00
(+) epigastric pain Neutrophils
(-) bleeding 59
Therapeutics: Omeprazole 20mg IV OD
(-) rashes
Lymphocytes 31
(+) full pulses
Monocytes 9
Dx: repeat CBC after hydration
I/O: 1730 (500)/900 VSq4h
Course in the Wards
October 06, 2019 (1 HD) Day 6 of Illness, Day 1 afebrile
Subjective Objective Plan
CBC Parameters Patient’s values Normal Value
BP: 90/60 mmHg
Hemoglobin
HR: 125-128 bpm 154 Diet for age; Avoidg/L
115-145 dark-colored foods
RR: 22-26 cpm
Hematocrit 43 33-43
RBC CountT: 36.2C 5.56 IVF: PLR 1L x 73 cc/hr (2cc/kg/hr)
4.00-5.30
(-) febrile episodes (+) flushed skin
Platelet 54 150-450
(+) epigastric
(-) bleeding WBC Count
tenderness 8.74 Therapeutics: Omeprazole 20mg IV OD
4.00-12.00
(+) epigastric pain Neutrophils
(-) bleeding 56
(-) rashes
Lymphocytes 30 Dx: repeat CBC
(+) full pulses
Monocytes 14
VSq4h
I/O: 2608 (1150)/1550
Course in the Wards
October 07, 2019 (2 HD) Day 7 of Illness, Day 2 afebrile
Subjective Objective Plan
CBC Parameters
BP: 90/60 mmHg Patient’s values Normal Value
HR: 118-128 bpm
Hemoglobin 129
Diet for age; Avoid dark-colored foods
115-145 g/L
RR: 24-32 cpm
Hematocrit 36 33-43
T: 36.7C IVF: PLR 1L x KVO
(+) flushed skin
RBC Count 4.61 4.00-5.30
(-) febrile episodes (+) slightly distended
Platelet 48 150-450
abdomen Therapeutics: ORS 1 sachet in 200ml water Q4h
(-) bleeding WBC(+)Count
minimal epigastric 5.31 4.00-12.00
Omeprazole 20mg IV OD
(-) epigastric pain tenderness
Neutrophils 50
Lymphocytes(-) bleeding 35
(-) rashes Dx: repeat CBC
Monocytes(+) full pulses 15

I/O: 1984 (1300)/2100 VSq4h

Course in the Wards
October 08, 2019 (3 HD) Day 8 of Illness, Day 3 afebrile
Subjective Objective Plan
CBC Parameters Patient’s values Normal Value
Hemoglobin 115
Diet for age; Avoid dark-colored foods
115-145 g/L
BP: 90/60 mmHg
Hematocrit 33 33-43
HR: 100-120 bpm IVF: PLR 1L x KVO
RBC Count 4.13 4.00-5.30
RR: 24-25 cpm
Platelet 49 150-450
No subjective T: 36.2C Therapeutics: ORS 1 sachet in 200ml water Q4h
WBC Count 3.91 4.00-12.00
complaints Unremarkable PE Omeprazole 20mg IV OD
Neutrophils 30
findings
Lymphocytes 50
Dx: Repeat CBC
Monocytes
I/O: 2216 (1900)/2000 19

VSq4h
Course in the Wards
October 09, 2019 (4 HD) Day 9 of Illness, Day 4 afebrile
Subjective Objective Plan
CBC Parameters Patient’s values Normal Value
Hemoglobin 124
Diet for age; Avoid dark-colored foods
115-145 g/L
BP: 90/60 mmHg
Hematocrit 36 33-43
HR: 98-105 bpm IVF: PLR 1L x KVO
RBC Count 4.51 4.00-5.30
RR: 22-25 cpm
Platelet 115 150-450
No subjective T: 36.8C Therapeutics: ORS 1 sachet in 200ml water Q4h
WBC Count 5.41 4.00-12.00
complaints Unremarkable PE Omeprazole 20mg IV OD
Neutrophils 25
findings
Lymphocytes 52
Dx: Repeat CBC
Monocytes
I/O: 1370 (1250)/1750 20

VSq4h
Course in the Wards
October 10, 2019 (5 HD) Day 10 of Illness, Day 5 afebrile
Subjective Objective Plan
CBC Parameters Patient’s values Normal Value
Hemoglobin 120 Diet for age; Avoidg/L
115-145 dark-colored foods
BP: 90/60 mmHg
Hematocrit 35 33-43
HR: 90-104 bpm IV4.00-5.30
access removed
RBC Count 4.30
RR: 21-23 cpm
Platelet 239 150-450
No subjective T: 36.4C
WBC Count 7.83Therapeutics: 4.00-12.00
ORS 1 sachet in 200ml water Q4h
complaints Unremarkable PE
Neutrophils 32
findings Dx: Repeat CBC
Lymphocytes 46
Monocytes
I/O: (1250)/1750 18
VSq4h
Course in the Wards
October 11, 2019 (6 HD) Day 11 of Illness, Day 6 afebrile
Subjective Objective Plan

No subjective Unremarkable PE
Patient may go home
complaints findings
CBC trends
CBC Parameters NV 10/05 10/05 (R) 10/06 10/07 10/08 10/09 10/10
Hemoglobin 115-145 g/L 176 162 154 129 115 124 120
Hematocrit 33-43 51 46 43 36 33 36 35
RBC Count 4.00-5.30 6.5 5.99 5.56 4.61 4.13 4.51 4.30
Platelet 150-450 50 34 54 48 49 115 239
WBC Count 4.00-12.00 5.67 6.98 8.74 5.31 3.91 5.41 7.83
Neutrophils 58 59 56 50 30 25 32
Lymphocytes 31 31 30 35 50 52 46
Monocytes 11 9 14 15 19 20 18
Eosinophils 1 2 3
Stabs 1 1
Basophils
Discussion
 Dengue
Flaviviridae
Flavivirus

Aedes aegypti or Aedes albopictus

 Current Dengue Situation in the Philippines

Most Affected Age Group: 5-9 years old (23%)

Most Affected Among Dengue Deaths: 5-9 years old (39%)
85%
Most Affected Regions: II, IV-A, V, VI, VII, VIII, IX, ARMM, NCR
higher
incidence CFR in WPR
than 2018 0.22%

WHO Philippines DENGUE OUTBREAK Situation Report, July 2019

Martina, B. E. E., Koraka, P., &
Osterhaus, A. D. M. E. (2009). Dengue
Virus Pathogenesis: an Integrated
View. Clinical Microbiology
Reviews, 22(4), 564–581. doi:
10.1128/cmr.00035-09
Clinical Features of Dengue Fever
Incubation period: 3-14 days
 Febrile phase
Symptoms: 2-7 days
• generalized body ache (+) Tourniquet test
• muscle and joint pains
(+) Progressive decrease in total white cell
• Headache count
• retro-orbital pain
• facial flushing
• sore throat, hyperemic pharynx
• macular or maculopapular rash
• petechiae and mild mucosal membrane
bleeding
Clinical Practice Guidelines on Dengue in Children; 2017 Philippine Pediatric Society and Pediatric Infectious Diseases Society of the Philippines
 Critical Phase
Day 3-7

Increase in capillary permeability in parallel

with increasing hematocrit levels may occur

The period of clinically significant plasma

leakage usually lasts 24–48 hours,

Clinical Practice Guidelines on Dengue in Children; 2017 Philippine Pediatric Society and Pediatric Infectious Diseases Society of the Philippines
Recovery Phase
Gradual improvement and stabilization of the hemodynamic status.

Clinical Practice Guidelines on Dengue in Children; 2017 Philippine Pediatric Society and Pediatric Infectious Diseases Society of the Philippines
Dengue Case Classification

Revised Dengue Clinical Case Management Guidelines 2011; Department of Health

 Diagnostics

Revised Dengue Clinical Case Management Guidelines 2011; Department of Health

Virological and Serological markers in relation to the time
of dengue infection

Revised Dengue Clinical Case Management Guidelines 2011; Department of Health

 Which patients warrant admission?
Shortness of breath
Irritability or drowsiness
Pleural effusion
Abdominal pain
Melena
Elevated hematocrit
Decreased or decreasing platelet count

Clinical Practice Guidelines on Dengue in Children; 2017 Philippine Pediatric Society and Pediatric Infectious Diseases Society of the Philippines
 Hemodynamic Assessment
Parameters Stable Condition Compensated Shock Hypotensive Shock
Sensorium Clear and lucid Clear and lucid Change of mental state
(restless, combative)

Capillary Refill Time Brisk (<2 sec) Prolonged (> 2 sec) Very prolonged, mottled
skin
Extremities Warm and Pink Cool peripheries Cold and clammy
Peripheral pulse volume Good volume Weak and thread Feeble or absent
Heart Rate Normal for age Tachycardia Severe tachycardia with
bradycardia in late shock
Clinical Practice Guidelines on Dengue in Children; 2017 Philippine Pediatric Society and Pediatric Infectious Diseases Society of the Philippines
 Hemodynamic Assessment
Parameters Stable Condition Compensated Shock Hypotensive Shock

Blood pressure Normal for age; Normal Normal systolic pressure Narrowed pulse
pulse pressure for age but rising diastolic pressure (<20mmHg)
pressure Hypotension
Narrowing pulse Unrecordable blood
pressure pressure
Postural hypotension
Respiratory Rate Normal for age Tachypnea Metabolic acidosis
hypopnea/ Kussmaul’s
breathing
Clinical Practice Guidelines on Dengue in Children; 2017 Philippine Pediatric Society and Pediatric Infectious Diseases Society of the Philippines
 Fluid Therapy
Ambulatory patients
Oral intake of oral rehydration solution, fruit juice and other fluids containing electrolytes
and sugar to replace losses from fever and vomiting.
Fluids containing high sugar or glucose should be avoided because they can exacerbate
hyperglycemia of physiological stress from dengue
Dengue fever with warning signs but without shock,
The recommendation is to give isotonic solutions such as 0.9% Saline or Ringer’s Lactate.

Clinical Practice Guidelines on Dengue in Children; 2017 Philippine Pediatric Society and Pediatric Infectious Diseases Society of the Philippines
Clinical Practice Guidelines on Dengue in
Children; 2017 Philippine Pediatric Society
and Pediatric Infectious Diseases Society of
the Philippines
Clinical Practice Guidelines on Dengue in
Children; 2017 Philippine Pediatric Society
and Pediatric Infectious Diseases Society of
the Philippines
Blood Transfusion
 Blood Products in Dengue Fever
Blood Dose Indication Remarks
Product
Fresh Whole 10-20 cc/kg Persistent and/or severe overt bleeding Decrease in Hct together with stable hemodynamic
Blood in the presence of unstable hemodynamic status and adequate urine
status; output indicates hemodilution and/or reabsorption of
extravasated fluids and does not warrant blood
Unstable hemodynamic status or transfusion.
refractory shock with decreasing Hct
despite adequate fluid administration Monitor hemodynamic status after blood transfusion;
repeat transfusion if there is
further blood loss or no appropriate rise in Hct after
blood transfusion.
Packed RBC 5-10 cc/kg Same as above PRBC is preferred over FWB if fluid overload is
present
Clinical Practice Guidelines on Dengue in Children; 2017 Philippine Pediatric Society and Pediatric Infectious Diseases Society of the Philippines
 Blood Products in Dengue Fever
Blood Dose Indication Remarks
Product
Fresh Frozen 10-20 cc/kg Massive bleeding not responsive to Do not give prophylactic FFP transfusions in the
Plasma transfusion of fresh whole blood or fresh absence of bleeding. FFP transfusion
packed cells leads to fluid overload because repeated and large
volume (40-50ml/kg) are needed for correction of
In cases of coagulopathy
coagulopathy with bleeding FFP transfusions do not produce sustained changes in
or suspected or confirmed the coagulation status and do not reduce the bleeding
DIC outcome in patients with
DHF/DSS.
Cryo- 1u/5kg Same as above Do not give prophylactic cryoprecipitate in the
precipitate absence of bleeding.
Cryoprecipitate contains fibrinogen, von Willebrand
factor, Factors 8 and 13;
less risk of fluid overload compared to FFP
 Blood Products in Dengue Fever
Blood Dose Indication Remarks
Product
Platelet 1u/10kg In patients with platelet count ≤ Prophylactic platelet transfusion is not
Concentrate 10,000/mm3. associated with systemic recommended in the absence of bleeding even at
massive bleeding or prolonged shock with levels ≤ 20,000/mm3.
bleeding not responsive to red cell
products (FWB or PRBC) or plasma
products
(FFP or cryoprecipitate)
There is insufficient evidence to recommend prophylactic platelet transfusion in children with dengue who have low platelet counts but who have no
significant bleeding.
There is insufficient data to show that platelet transfusion prevents progression to severe bleeding or reduces risk of subsequent bleeding, hastens
platelet recovery, reduces hospital stay, or decrease risk of mortality.

Clinical Practice Guidelines on Dengue in Children; 2017 Philippine Pediatric Society and Pediatric Infectious Diseases Society of the Philippines
When do we discharge dengue patients?
 Discharge Criteria
ALL must be present:

No fever for 48 hours

Improvement in clinical status
Increasing trend of platelet count
Stable hematocrit without intravenous fluids

Revised Dengue Clinical Case Management Guidelines 2011; Department of Health

CBC trends
CBC Parameters NV 10/05 10/05 (R) 10/06 10/07 10/08 10/09 10/10
Hemoglobin 115-145 g/L 176 162 154 129 115 124 120
Hematocrit 33-43 51 46 43 36 33 36 35
RBC Count 4.00-5.30 6.5 5.99 5.56 4.61 4.13 4.51 4.30
Platelet 150-450 50 34 54 48 49 115 239
WBC Count 4.00-12.00 5.67 6.98 8.74 5.31 3.91 5.41 7.83
Neutrophils 58 59 56 50 30 25 32
Lymphocytes 31 31 30 35 50 52 46
Monocytes 11 9 14 15 19 20 18
Eosinophils 1 2 3
Stabs 1 1
Basophils
Recent Updates on Dengue vaccines
Dengue vaccine: Global development update. (2019). Asian Pacific Journal of Allergy and Immunology. doi: 10.12932/ap-100518-0309
 • Sanofi-Pasteur
• Only licensed vaccine
• Live-attenuated tetravalent chimeric
vaccine that incorporates structural
genes into the genome of yellow
fever vaccine
• 9 years and older

• Seronegativity placed children at

higher risk of acquiring severe
hospitalized dengue

Dengvaxia®
Halstead, S. B., & Dans, L. F. (2019). Dengue infection and advances in dengue vaccines for children. The Lancet Child & Adolescent Health, 3(10), 734–741. doi: 10.1016/s2352-
Antibody Dependent Enhancement
 • Live-attenuated DENV-2 strain and
three chimeric viruses
• DENV-1 and 2 from Thailand
• DENV-3 from the Philippines
• DENV-4 from Indonesia

• Non-structural proteins

TAK-003
Halstead, S. B., & Dans, L. F. (2019). Dengue infection and advances in dengue vaccines for children. The Lancet Child & Adolescent Health, 3(10), 734–741. doi: 10.1016/s2352-
 Magnitude and Functionality of the NS1-Specific Antibody
Response Elicited by a Live-Attenuated Tetravalent Dengue
Vaccine Candidate (TAK-003)
• Increased DENV-2 NS1-specific IgG in naive individuals
• (+) cross-reaction with DENV-1, -3, and -4 NS1 to varying extents.
• All samples from naïve and preimmune vaccinees completely abrogated DENV-2 NS1-
induced hyperpermeability and cross-inhibited hyperpermeability induced by DENV-1, -3,
and -4 NS1.
• Inhibition of NS1-induced hyperpermeability correlated with NS1-specific IgG
concentrations.
• Postvaccination sera also prevented NS1-induced degradation of endothelial glycocalyx
components.
Sharma, M., Glasner, D. R., Watkins, H., Puerta-Guardo, H., Kassa, Y., Egan, M. A., … Harris, E. (2019). Magnitude and Functionality of the NS1-Specific Antibody
Response Elicited by a Live-Attenuated Tetravalent Dengue Vaccine Candidate. The Journal of Infectious Diseases. doi: 10.1093/infdis/jiz081
 References
• Clinical Practice Guidelines on Dengue in Children; 2017 Philippine Pediatric Society and Pediatric
Infectious Diseases Society of the Philippines
• Dengue vaccine: Global development update. (2019). Asian Pacific Journal of Allergy and Immunology. doi:
10.12932/ap-100518-0309
• Halstead, S. B., & Dans, L. F. (2019). Dengue infection and advances in dengue vaccines for children. The
Lancet Child & Adolescent Health, 3(10), 734–741. doi: 10.1016/s2352-4642(19)30205-6
• Martina, B. E. E., Koraka, P., & Osterhaus, A. D. M. E. (2009). Dengue Virus Pathogenesis: an Integrated
View. Clinical Microbiology Reviews, 22(4), 564–581. doi: 10.1128/cmr.00035-09
• Revised Dengue Clinical Case Management Guidelines 2011; Department of Health
• Sharma, M., Glasner, D. R., Watkins, H., Puerta-Guardo, H., Kassa, Y., Egan, M. A., … Harris, E. (2019).
Magnitude and Functionality of the NS1-Specific Antibody Response Elicited by a Live-Attenuated
Tetravalent Dengue Vaccine Candidate. The Journal of Infectious Diseases. doi: 10.1093/infdis/jiz081
zzzzzzzzzzzzzzzzzzzzzz