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Case
1
A 4 month old baby girl presented
with high grade fever and runny nose for four days associated with bilateral
lower limb and back petichiae rash and diarrhea for 1 day duration. Upon admission,
patient was on day four of illnesses. She was conscious and alert, responding
to stimuli, good hydration and perfusion status, mild pallor, good capillary
refilling time and active. Apart from that, she also had a palpable liver 3 cm
from the costal margin and 2 cm spleen palpable. Examination of the other
systems was unremarkable. Blood
investigation results were as follows. Hb 10.9, TWBC 13.2 with predominant of
neutrophils, platelet 37, hematocrit 37. PT 12.7, PTT 55.4, INR 1.14. LDH 1467,
CK 154, Total bilirubin 8.9, Alt 221, ALP 254, Protein 61, Albumin/Globulin
36/25. BSMP negative. Peripheral blood smear did not show any abnormal
morphology of blood cell except for the reducing number of platelets. Dengue
serology IgM and NS-1 antigen taken on day 5 of illness are both positive. Patient
was treated as dengue fever with acute liver injury and discharged well on D10
of illness.
Case
2
3 months old baby boy who was
recently move to Tawau town was brought to hospital for high grade fever for 3
days, petichiae body rashes and less active. Upon presentation, patient was conscious
and alert but weak looking, not septic looking, and mild dehydrated and stable
vital sign. He was given fluid resuscitation and admitted to pediatric intensive
care unit in view of suspicious for dengue. Other physical examinations are un
remarkable. FBC result shows Hb 10, TWBC 22, Pla 28, and PCV 34. PT 13, PTT 60,
INR 1.3. BSMP was negative and IgG and IgM serology were both positive. Other
blood paramenters were normal. He was treated as dengue fever and was closely
monitored for possibility of dengue shock syndrome / dengue hemorrhagic fever. After
receiving symptomatic treatment and prophylactic FFP transfusion, platelet
transfusion and vitamin K for three days, he made an uneventful recovery and
discharged on D10 of illness.
Case
3
8 years old girl with no known
medical illness presented with fever for 4 days associated with abdominal pain,
vomiting, passing out loose stool and excessive thirst. Upon examination, she was
conscious but agitated, mild pallor, dehydrated, cold periphery, tachycardic
with good pulse volume and normal BP. After given a 500 cc of fluid challenge,
the BP drop and she was further managed with fluid resuscitation and transferred
to pediatric intensive care unit for close monitoring. A lab result came back
with severe metabolic acidosis, LDH 700, CK 1000. Hb 15, TWBC 16, platelet 70
PCV 54. BSMP was negative. Dengue serology was positive for both IgG and IgM. She
was then subsequently intubated for airway protection in view of drowsiness and
increase in restlessness. Unfortunately, the patient was complicated with
massive upper GI bleed, severe metabolic acidosis, acute kidney injury, acute
liver injury, hyperkalaemia from massive blood product transfusion, ventricular
tachycardia and later develops ventricular fibrillation and asystole. Despite of extensive resuscitation effort with
fluid management, triple inotropic agent, blood product transfusion and
cardiopulmonary resuscitation for two times with defibrillation and
cardioversion, she was pronounced death after 10 hours of admission. The cause
of death was dengue hemorrhagic fever with severe metabolic acidosis and
multiple organ failure.
Discussion
We currently have two Malaysian
guidelines on dengue which is one for adult (revised 2010) and pediatric
(2004). In guidelines, normal white cell count or leucopenia are put under
laboratory test that should be raised suspiciousness for dengue fever, together
with rising hematocrit or thrombocytopenia. Both of these guidelines are not
yet updated.
If we look at the section
concerning laboratory finding for dengue hemorrhagic fever in WHO guidelines
(1997), white blood cells count may be variable at the onset of illness, ranging
from leucopenia to mild leukocytosis, but a drop in the total white- blood-cell
count due to a reduction in the number of neutrophils is virtually always
observed near the end of the febrile phase of illness. Relative lymphocytosis,
with the presence of atypical lymphocytes, is a common finding before defervescence
or shock.
However, in all latest WHO guidelines
like update on dengue (2009), comprehensive guidelines (2011) and handbook of
dengue (2012), the phrase concerning TWBC or leucopenia was not highlighted
except in a section for probable dengue case. The only hematological parameters
that are highly suggestive of dengue are raising hematocrit and
thrombocytopenia during the resolving of febrile phase.
Data from L. Kittigul et al (2007)
based on 1 year study period from Sept 2013-August 04 in 286 dengue patient
admitted to Phetchabun Provincial Hospital Thailand shows that TWBC value in children
is (5.7+14) and adult (4.7+2.9)
According to P.L. Lu et al (2004), Leucopenia
is found in most non shock cases of dengue infection. Only 16% of mild cases
have leukocytosis, which appears during the recovery stage, whereas 67% of
shock cases and 66% of mortality cases have pronounced leukocytosis
In other study, they even found
that leukocytosis in dengue is suggestive of superimposed bacterial infection
and even posing a greater mortality rate if not treated.
Based on the three cases that I mentioned
earlier together with the evidence based text, I think, it is a time for a
clinician to put aside their ego and looking at things seriously when receive a
referral for to rule out dengue in a patient with thrombocytopenia and
hemoconcentration even with the presence of leukocytosis. Yes, it could be due
to many other causes including typhoid, leptospirosis or tick born disease or
even severe sepsis, but dengue should not be neglected if the history is
suggestive and patient is from endemic area of dengue.
As a conclusion, dengue should
divorce with leucopenia and remain as a loyal husband to rising hematocrit
concentration and thrombocytopenia and they should be blessed with dengue
serology investigation once present.
Reference:
1. Dengue hemorrhagic fever : diagnosis, treatment,
prevention and control 2nd edition, WHO 1997
2. Clinical Practice Guidelines on Management of
Dengue Fever in Children, Ministry of health Malaysia 2004
3. Clinical Practice Guidelines on Management of
Dengue Infection in Adult, Revised 2nd edition, ministry of health Malaysia
2010
4. Dengue: guidelines for diagnosis, treatment,
prevention and control -- New edition., WHO 2009
5. Comprehensive Guidelines for Prevention and
Control of Dengue and Dengue Hemorrhagic Fever, Revised and expanded edition:
WHO 2011.
6. Handbook for clinical management of dengue, WHO 2012
7. Leera Kittigu et al, "The differences of
clinical manifestations and laboratory findings in children and adults with
dengue virus infection", Journal of Clinical Virology 39 (2007) 76–81,
Elsevier 2006
8. Po-Liang Lu, Hui-Hwa Hsiao et al, "Dengue
Virus-Associated Hemophagocytic Syndrome And Dyserythropoiesis: A Case Report",
Kaohsiung J Med Sci 2005;21:34–9), Elsevier 2005
