Dengue infection can be either asymptomatic, or progress to involve hemorrhagic manifestations with shock [1]. Thrombotic events have not been extensively reported, despite the wide range of increased procoagulant activity during illness [2,3].

An 11-year-old boy presented with high grade fever for past 7 days, headache, arthralgia, myalgia, nausea, abdominal pain and right calf pain. Examination revealed stable vitals, mild pallor, soft tender hepatomegaly, right calf swelling, and tenderness with positive Homan’s sign. There was no evidence of capillary leak. His hemogram revealed normocytic normochromic anemia, haematocrit 49%, TLC 9500/cu mm and platelet count of 1,60,000/cu. mm. His liver function tests showed mildly increased transaminases (SGOT 119 IU/mL, SGPT 171 IU/mL); serum urea and creatinine levels were normal. Ultra-sonography (USG) with colour Doppler study of right leg showed extensive thrombosis with no color flow involving right popliteal; right superficial, deep, common femoral vein with proximal extension upto external iliac vein

There was no history of venous catheter placement in his lower limbs or any past history or family history suggestive of venous thromboembolism. D-dimer was increased (6694 ng/mL). Malaria parasite antigen test, blood culture and Widal test were negative. Coagulation studies and routine stool examination yielded normal results.Hepatitis A, B, C virus infections were ruled out serologically. But, he was serologically confirmed positive for anti-DEN 1 IgM by IgM antigen capture enzyme-linked immunosorbent assay on day 6 of illness.

Screening for inherited thrombophilia did not reveal any abnormality. He was screened for Protein C,S deficiency and prothrombin mutation analysis done. Echocardiography and Doppler ultrasonography of portal and mesenteric veins was normal.

Keeping in view the risks of life threatening pulmonary embolism and because his PT, APTT and TT reports and platelet counts were within normal ranges, he was started on subcutaneous enoxaparin 1 mg/kg/day in 2 divided doses with twice weekly monitoring of platelet counts, APTT levels and USG and weekly peak anti-Xa levels maintained between 0.5 and 1.0 IU/mL. After 12 days, USG with color Doppler of ileo-femoral venous system showed decreased extent of the thrombus. After 2 weeks of subcutaneous heparin, he was started on oral warfarin keeping INR between 2-3. After 4 weeks, the veins were completely recanalized and his anticoagulation therapy was discontinued after 3 months.

Many factors might increase thrombotic risk in children with dengue fever [2, 3]. Dengue virus may down regulate thrombomodulin-thrombin-protein C complex formation thus reducing activated protein C [4]. Low concentrations of plasma anticoagulant proteins C and S and antithrombin III have been detected in severe dengue but have not been associated with clinical thrombosis [3]. No procoagulant risk factor was identified in this case.

Dengue virus activates endothelial cells and increases the expression of thrombomodulin [5]. Lin, et al. [6] described host antibodies formed against dengue non-structural protein that had cross-reactivity with host endothelial cells which can lead to inflammatory responses. Increased PAI-1 plasma levels were also observed [3]. Disseminated intravascular coagulation and consequent microthombi formation may contribute but have not been associated with large vessel thrombosis [2]. Antibodies against phospholipids, cardiolipin and increased lupus anticoagulant have been associated with thrombotic events in peripheral arteries and cerebral vasculature [7]. Venous cerebral vasculature thrombosis and ischemic stroke not associated with any risk factor have been rarely reported in dengue fever [8]. As the thrombosis was clinically detected at admission, loss of endothelium non-thrombogenic protective factors may have been the cause [2].

There are only a handful of reported cases where deep vein thrombosis have been reported in direct association with dengue fever [2,7]. Thrombotic events in large veins [ileo-femoral deep vein thrombosis (DVT), pulmonary thromboembolism, mesenteric vein thrombosis] in DF patients have been reported from Brazil in 5.4% of all dengue inpatients.

The dilemmas posed in treating a blood clot in a patient who is at risk for excessive bleeding were challenging.

Awareness for these thrombotic complications is recommended to all practitioners who treat dengue in hospital settings

Contributors: AR and JC: did the patient work up and drafted the manuscript; SC critically reviewed the manuscript. The final manuscript was approved by all authors.

Funding: None; Competing interests: None stated.

1. Pandy G. Prevalence of dengue infections in India. Def Sci J. 1982;l32:359-70.

2. Mairuhu AT, MacGillavry MR, Setiati TE, Soemantri A, ten Cate H, Brandjes DP, et al. Is clinical outcome of dengue virus infections influenced by coagulation and fibrinolysis? A critical review of the evidence. Lancet Infect Dis. 2003;3:33-41.

3. Mairuhu AT, Setiati TE, Koraka P, Hack CE, Leyte A, Faradz SM, et al. Increased PAI-1 plasma levels and risk of death from dengue: no association with the 4G/5G promoter polymorphism. Thromb J. 2005;3:17.

4. Cabello-Gutiérrez C, Manjarrez-Zavala ME, Huerta-Zepeda A, Cime-Castillo J, Monroy-Martínez V, Correa BB, et al. Modification of the cytoprotective protein C pathway during dengue virus infection of human endothelial vascular cells. Thromb Haemost. 2009;101:916-28.

5. Chen LC, Shyu HW, Lin HM, Lei HY, Lin YS, Liu HS, et al. Dengue virus induces thrombomodulin expression in human endothelial cells and monocytes in vitro. J Infect. 2009;58:368-74.

6. Lin CF, Wan SW, Cheng HJ, Lei HY, Lin YS. Autoimmune pathogenesis in dengue virus infection. Viral Immunol. 2006;19:127-32.

7. Karunatilaka DH, De Silva JR, Ranatunga PK, Gunasekara TM, Faizal MA, Malavige GN. Idiopathic purpura fulminans in dengue hemorrhagic fever. Indian J Med Sci. 2007; 61:471-3.