|Year : 2015 | Volume
| Issue : 1 | Page : 51-53
Platelet phagocytosis in peripheral blood during acute phase of dengue virus infection
Nidhya Ganesan, Indira Gunasekaran, Somanath Padhi, Anita Ramdas, Manjiri Phansalkar
Department of Pathology, Pondicherry Institute of Medical Sciences, Puducherry, India
|Date of Submission||31-May-2015|
|Date of Acceptance||15-Jul-2015|
|Date of Web Publication||9-Nov-2015|
Department of Pathology, Pondicherry Institute of Medical Sciences, Puducherry
Source of Support: None, Conflict of Interest: None
We aimed to describe peripheral blood phagocytosis of platelets as a possible underlying mechanism of thrombocytopenia during the acute phase of dengue virus infection in a young male. Furthermore, enhanced platelet phagocytosis through the apoptotic mechanism is also briefly highlighted.
Keywords: Apoptosis, dengue virus, peripheral blood, phagocytosis, thrombocytopenia
|How to cite this article:|
Ganesan N, Gunasekaran I, Padhi S, Ramdas A, Phansalkar M. Platelet phagocytosis in peripheral blood during acute phase of dengue virus infection. J Curr Res Sci Med 2015;1:51-3
|How to cite this URL:|
Ganesan N, Gunasekaran I, Padhi S, Ramdas A, Phansalkar M. Platelet phagocytosis in peripheral blood during acute phase of dengue virus infection. J Curr Res Sci Med [serial online] 2015 [cited 2019 May 25];1:51-3. Available from: http://www.jcrsmed.org/text.asp?2015/1/1/51/168929
| Introduction|| |
Dengue, a Flavivirus and transmitted by Aedes aegypti mosquito, is a great public health concern in India. Over the last decade, dengue has reached pan-Indian epidemic proportions leading to significant morbidity and mortality. Four serotypes of dengue virus (DENV) are known to cause the disease such as DENV-1, DENV-2, DENV-3, and DENV-4. A protective immunity against one infecting serotype lasts lifelong, but this is very short lasting (3–4 months) against other serotypes. Therefore, the second infection after the protective period often results in severe disease.
Thrombocytopenia and increased vascular permeability are the two major characteristics of dengue fever (DF). As per 2009 WHO recommendation, dengue cases can be classified into: (i) dengue without warning signs, (ii) dengue with warning signs (abdominal pain/persistent vomiting/mucosal bleed/increase in hematocrit with decrease in platelet count), and (iii) severe dengue (severe plasma leakage, severe bleeding, and severe organ involvement). Thrombocytopenia associated with dengue infection is postulated to have has several underlying mechanisms. In this manuscript, we aimed to describe the occurrence of platelet phagocytosis by peripheral blood monocytes, and highlight apoptosis-phagocytosis as another mechanism of dengue associated thrombocytopenia.
| Case Report|| |
A 19-year-old male college student was evaluated for a 3-day history of high-grade fever, generalized myalgia, and the loss of appetite. He had no organomegaly, lymphadenopathy, skin rash, or any bone tenderness. His routine laboratory evaluation, on day 2 postadmission, showed hemoglobin - 130 g/L (reference 120–140 g/L), hematocrit - 43% (37–54%); total leukocyte count - 6 × 109/L with differentials of neutrophil - 40%, lymphocytes - 55%, and monocytes - 5%; total platelet count - 60 × 109/L (150–450 × 109/L), mean platelet volume - 11 fL (6–11 fL), and platelet distribution width - 23% (11–18%). Leishmann stained peripheral smear evaluation revealed normocytic normochromic red cells, relative lymphocytosis with reactive lymphoid cells, thrombocytopenia with numerous giant platelets, and no blasts. Besides these, there was an evidence of platelet phagocytosis by monocytes [Figure 1], ×400]. His biochemical parameters showed raised liver transaminases (serum glutamic-oxaloacetic transaminase - 105 IU/L, serum glutamic pyruvic transaminase - 115 IU/L, reference < 50 IU/L), and coagulation parameters were within normal reference range. His microbiological workup for HIV, hepatitis B and C viruses, Salmonella, scrub typhus, malaria, and leptospira were negative. DENV serology revealed positive nonstructural antigen-1 by ELISA. He was managed symptomatically and finally discharged on 8th-day postadmission with a platelet count of 100 × 109/L, and his liver transaminases at the time of discharge were 65 and 59 IU/L, respectively.
|Figure 1: Peripheral blood smear from a young male patient with acute phase dengue virus infection demonstrating platelet phagocytosis by monocytes (black arrow). The platelet count at the time of admission was 60 × 109/L. Note the presence of a giant platelet (back arrow head) and a reactive lymphoid cell at the right lower corner of the field (Leishmann, ×400)|
Click here to view
| Discussion|| |
The proposed mechanisms of DENV associated thrombocytopenia are: (i) DENV induced direct suppression of bone marrow megakaryopoiesis, and (ii) Immune-mediated increased the peripheral destruction. An increased level of platelet associated IgG is frequently observed in patients with chronic idiopathic thrombocytopenic purpura. The previous studies have also found an inverse correlation between the levels of platelet associated antibodies and platelet count during the acute phase of dengue infection. It is hypothesized that increased macrophage clearance of peripheral platelets (coated with immune complexes) through both Fc receptor and complement receptor mechanisms, as well as direct platelet lyses, are the likely causes of thrombocytopenia in these patients.
Recent in-vitro studies on dengue patients have shown that DENV induces increased peripheral platelet clearance by phagocytosis secondary to the apoptotic mechanism, during the acute and early convalescence phases of the infection., By using flow cytometry, it was demonstrated that compared to healthy volunteers (n = 38), platelets isolated from dengue patients (57 with DF, 24 with dengue hemorrhagic fever [DHF]) showed significantly higher (P < 0.001) upregulation of proapoptotic markers such as active caspase-3 on their membranes (2.82 ± 1.05% vs. 16.82 ± 11.31%, respectively), increased Annexin V binding (3.27 ± 0.91% vs. 19.67 ± 10.72%, respectively); and thus increased phagocytosis by macrophages (20.29 ± 5.77% vs. 55.46 ± 29.66%, respectively). Furthermore, these findings were significantly (P < 0.05) observed from patients with DHF than those from DF. The outcome of the above study is intriguing because of the very fact that platelet being anucleate particles lacks the machinery to express the apoptotic genes! Hence, the detailed molecular mechanism of DENV induced peripheral phagocytosis of activated platelets remains to be fully understood. As suggested by Honda et al., the percentage of phagocytosis should be correlated with platelet associated immunoglobulin titers.
Our observation of peripheral platelet phagocytosis, in the present case, supports the hypothesis that increased peripheral clearance is an important mechanism in DENV associated thrombocytopenia. More prospective studies are required to validate the apoptotic hypothesis as suggested by Alonzo et al. However, we do suggest that platelet phagocytosis in peripheral blood should be mentioned, as well as quantified, in clinical pathology reporting in cases with dengue associated thrombocytopenia.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Cecilia D. Current status of dengue and chikungunya in India. WHO South East Asia J Public Health 2014;3:22-7.
de Castro RA, de Castro JA, Barez MY, Frias MV, Dixit J, Genereux M. Thrombocytopenia associated with dengue hemorrhagic fever responds to intravenous administration of anti-D (Rh(0)-D) immune globulin. Am J Trop Med Hyg 2007;76:737-42.
Cecilia D, Shah PS, Alagarasu K. Dengue: Achievements in the last decade. In: Arankalle VA, Cecilia D, editors. NIV Golden to Diamond Jubilee: The Glorious Decade. Pune, India: Golden Jubilee Publication; 2012. p. 141-62.
Martina BE, Koraka P, Osterhaus AD. Dengue virus pathogenesis: An integrated view. Clin Microbiol Rev 2009;22:564-81.
La Russa VF, Innis BL. Mechanisms of dengue virus-induced bone marrow suppression. Baillieres Clin Haematol 1995;8:249-70.
Rand ML, Wright JF. Virus-associated idiopathic thrombocytopenic purpura. Transfus Sci 1998;19:253-9.
Saito M, Oishi K, Inoue S, Dimaano EM, Alera MT, Robles AM, et al.
Association of increased platelet-associated immunoglobulins with thrombocytopenia and the severity of disease in secondary dengue virus infections. Clin Exp Immunol 2004;138:299-303.
Alonzo MT, Lacuesta TL, Dimaano EM, Kurosu T, Suarez LA, Mapua CA, et al.
Platelet apoptosis and apoptotic platelet clearance by macrophages in secondary dengue virus infections. J Infect Dis 2012;205:1321-9.
Honda S, Saito M, Dimaano EM, Morales PA, Alonzo MT, Suarez LA, et al.
Increased phagocytosis of platelets from patients with secondary dengue virus infection by human macrophages. Am J Trop Med Hyg 2009;80:841-5.