Spontaneous central vein thrombosis in a patient with activated protein C resistance and dengue infection: An association or causation?
A 21-year-old non-obese female patient with no co-morbid illness was referred to our intensive care unit (ICU) from a private hospital with history of high grade fever with chills 8 days back with respiratory distress for 6 days and altered sensorium for 2 days. She was apparently healthy, unmarried, and had no history of hormone intake. She was intubated for altered sensorium and had already received mechanical ventilation for 48 hours. She was referred to us in a state of shock with vasopressors infusions on flow (dopamine through peripheral line). Additionally, she had edematous peripheries (right upper limb swelling was more as compared to the left). She had leukocytopenia (2,400/cmm), thrombocytopenia (20,000/cmm), and normal prothrombin time, activated partial thromboplastin, and thrombin times and fibrinogen levels. Neck ultrasonography (USG) prior to an attempt of right IJV cannulation revealed a non-compressible right IJV along with absence of venous flow in color Doppler strongly suggestive of right IJV thrombus. Her left IJV and SCV were compressible (checked by using linear ultrasound probe supraclavicularly) and patent, hence we inserted the central line in the left SCV for hemodynamic monitoring, fluid resuscitation and vasopressor use. Radiologists evaluated and confirmed right IJV thrombus with extension towards right SCV. Her lower limb Doppler study was, however, within normal limits. Echocardiography showed mild tricuspid regurgitation with ejection fraction <55% with mild dilatation of main pulmonary arteries. Urgent thoracic computed tomography (CT) angiography revealed left distal pulmonary artery thrombosis []. We immediately started unfractionated heparin (loading dose: 80 U/kg followed by continuous infusion @ 20 U/kg/hr.) to achieve a target activated partial thromboplastin time (APTT) of 2-2.5 times the normal. Further investigations demonstrated APC-R using the test kit STA -staclot APC-R (Diagnostica Stago, Asnieres, France) and genetic markers for thrombosis using polymerase chain reaction showed homozygous to Factor V Leiden mutation. After achieving the target APTT, oral vitamin K anticoagulants (OVKA) in the form of warfarin 5 mg was started along with the heparin to aim international normalized ratio (INR) of 2-2.5. We achieved target INR within next 5 days. Then, heparin was stopped and warfarin was continued. Her other supportive management included fluids, sedation, vasopressors, broad spectrum antibiotics, enteral nutrition, and mechanical ventilation. In the meantime, Dengue IgM Enzyme-linked immunosorbent assay (ELISA) (Dengue IgM capture ELISA, PanBio, Australia) was also found to be positive. Within the next week her hemodynamic status improved and she could be weaned off from the ventilator. After the shock recovered, we did thrombophilia testing of this patient []. Her swelling of the right upper limb was regressed gradually. But, her right IJV and SCV thrombus persisted with partial recanalization in follow up USG []. She was discharged on oral warfarin treatment. She is now under our follow-up. Importantly, her father, mother, and younger sister underwent factor 5 Leiden mutation test which was tested negative.