May 17, 2013

Is Dengue Married to Leucopenia: An Experience with Three Atypical Dengue Cases

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.


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.


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

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