Dengue is an infectious disease caused by the Arbo virus of the flaviviridae type spread by the Aedes mosquito. The clinical features of dengue range from acute undifferentiated fever in a mild form, classically known as dengue fever, to the severe clinical and potentially fatal Dengue hemorrhagic fever/ Dengue shock syndrome. Thrombocytopenia is a major and common finding seen in both mild and severe cases and it is significantly proportionate with of severity of dengue progression. Severe illness is characterized by hemodynamic changes, increased vascular permeability, hypovolemia and shock. Thrombocytopenia and platelet dysfunction are commonly seen in dengue and are related to the outcome. Different mechanisms have been hypothesized to explain DENV-associated thrombocytopenia, includes bone marrow suppression and peripheral platelets destruction.
37year gentlemen, already diagnosed to have type II Diabetes mellitus, systemic hypertension and hypothyroid presented with complaints of high grade fever associated with chills and rigors and giddiness from day one. On arrival, the patient was alert, tachycardic (130bpm), hypotensive (60/40 mmHg) and febrile (103.4′). His blood investigations revealed leucopenia, thrombocytopenia with Dengue NS1Ag: POSITIVE initially, and later Dengue IGM and IGG became positive. During the course of the illness the patient’s hematocrit increased, thrombocytopenia worsened. The hypotension persisted which was managed accordingly with IV fluids and Ionotropic support. After 8 days of illness, the patient became normotensive with an increasing trend of platelets andnormalization of hematocrit. The patient was weaned off ionotropic support and was symptomatically better.
DENGUE: GENERAL ASPECTS
Dengue viruses are the most important human arboviruses worldwide and are transmitted by mosquitoes of the genus Aedes in the form of four distinct serotypes (DENV-1, DENV-2, DENV-3, and DENV-4). Dengue causes serious infection in humans, resulting in morbidity and, at times, mortality in most tropical and subtropical areas of the world. Dengue viruses are members of the Flaviviridae family, which are single-stranded RNA viruses. The nonstructural proteins are involved in viral translation, transcription, and replication. NS1 is a protein involved in viral RNA replication and is expressed on the surface of infected cells. NS1 Antigen in blood correlates with the viral titters and has been a useful tool in the diagnosis of dengue infection, because it is expressed on the surface of infected cells and NS1 triggers host immune responses, it is involved in the dengue pathogenesis.
PHASES OF DENGUE:
CLASSIFICATION OF DENGUE:
DIAGNOSIS AND MANAGEMENT WHO 2009 GUIDELINES
GRADING SEVERITY OF DHF:
Platelets and hematocrit values are usually measured during the acute stages of dengue infection. A drop of the platelet count below 1,00000 per µL may be seen but a decreasing trend is seen commonly in dengue hemorrhagic fever. Thrombocytopenia is usually observed in the period between day 3 and day 8 following the onset of illness. Thrombocytopenia serves as a clinical tool in the early diagnosis of dengue infection. Hemoconcentration, estimated an increase in hematocrit of 20% or more compared with convalescent values, is suggestive of hypovolaemia and it is due to vascular permeability and plasma leakage.
At present, the three basic methods used in the diagnosis of dengue virus infection are viral isolation, detection of the viral genomic sequence by a nucleic acid amplification technology assay (Reverse transcription polymerase chain reaction (RT-PCR)), and detection of dengue virus-specific IgM antibodies by the enzyme-linked immunosorbent assay (MAC-ELISA) and/or the rapid dengue immunochromatographic test (ICT).Detection of NS1 has been a confirmatory test to diagnose dengue in its febrile stage. The NS1 protein was found to be highly present in all dengue serotypes, circulating in high levels during the first few days of illness.
SOURCE: DENGUE DIAGNOSIS AND MANAGEMENT WHO 2009 GUIDELINES
WHY THROMBOCYTOPENIA IN DENGUE???
SOURCE: DENGUE DIAGNOSIS AND MANAGEMENT WHO 2009 GUIDELINES
In 2009 WHO guidelines, Thrombocytopenia is defined as the rapid decline in platelet count or a platelet count of less than 150,000 per microliter of blood. The mechanism involved in dengue directly or indirectly affects bone marrow progenitor cells by inhibiting their function and reducing the proliferative capacity of hematopoietic cells. There is evidence that DENV can induce bone marrow hypoplasia during the acute phase of the disease, irrespective of platelets counts. The functional disruption of these cells is associated with a significant dysregulation of the plasma kinin system. In addition, DENV infection induces platelet consumption due to disseminated intravascular coagulation (DIC), platelet destruction due to increased apoptosis, lysis by the complement system and by the involvement of antiplatelet antibodies.
WHEN TO MANAGE THROMBOCYTOPENIA?
Thrombocytopenia has been one of the criteria used by WHO guidelines as an indicator of clinical severity of illness. Platelet counts in DHF/DF tend to decrease from the 4th day of the illness until the 7th day and reach normal levels on the 8th or 9th day. Clinical guidelines recommend platelet transfusions be indicated to patients who develop serious hemorrhagic manifestations or, have platelet counts falling below 10000 /cu.mm without hemorrhage or 50000/cu.mm with bleeding or hemorrhage. The efficacy of platelet transfusions is controversial. Platelet transfusions should not be routinely used in the management of dengue fever unless indicated. Patients who received transfusion have a higher chance of developing pulmonary edema and requiring increased hospitalization. Platelet transfusion does not prevent the development of severe bleeding.
OTHER SEVERITY MARKERS IN DENGUE:
Coagulopathy and vasculopathy are other hematological abnormalities apart from thrombocytopenia generally observed in severe dengue. Patients with allergies or diabetes are at 2.5 times greater risk of developing Dengue Hemorrhagic fever. Moreover, complications of dengue fever are higher with patients suffering from hepatitis. Hyperferritinemia is known to be associated with clinical disease severity and is currently used as a laboratory marker for dengue. The coagulation and fibrinolytic systems are highly activated in dengue patients with hyperferritinemia. Furthermore, cytokines and coagulation mediators mediate the inflammatory response, promoting increased interaction between immune cells, platelets, and ECs, contributing to thrombocytopenia.
Dengue fever causes various hematological and biochemical abnormalities. Monitoring the severity of dengue is of paramount importance in the management of the disease. Even though thrombocytopenia might not be present at the time of initial evaluation and there are other markers to assess the severity, it still continues to be the most important and convenient marker in assessing the severity of the illness.
1.WHO, Dengue Haemorrhagic Fever: Diagnosis, Treatment, Prevention and Control, World Health Organization: WHO, Geneva, Switzerland, 2nd edition, 2018, http://www.who.int/csr/resources/publications/dengue/Denguepublication/en/.
2.Predictors of Major Bleeding and Mortality in Dengue Infection: A Retrospective Observational Study in a Tertiary Care Centre in South India
3.Correlation of serological markers and platelet count in the diagnosis of Dengue virus infection
4.IMAGES:DENGUE DIAGNOSIS AND MANAGEMENT WHO 2009 GUIDELINES.
Dr. Jothimeena. N
Department Of Critical Care
Kauvery Hospital Chennai