A case of pulmonary thromboembolism due to coagulation factor V Leiden in Japan ~ usefulness of next generation sequencing~
© The Author(s). 2017
Received: 19 January 2017
Accepted: 7 March 2017
Published: 14 March 2017
Because the venous thromboembolisms (VTEs) due to the coagulation factor V R506Q (FV Leiden) mutation is often seen in Caucasians, the VTE onset in Japan has not been reported.
A 34-year-old man from north Africa experiencing sudden dyspnea went to a hospital for advice.
The patient had pain in his right leg and a high plasma D-dimer level. A contrast-enhanced computed tomography scan revealed a contrast deficit in the bilateral pulmonary artery and in the right lower extremity. The patient was diagnosed with VTE, and anticoagulation therapy was initiated. Our targeted gene panel sequencing revealed that the occurrence of VTE was attributed to a presence of the FV Leiden mutation.
This is the first report demonstrating VTE caused by the FV Leiden mutation in Japan.
KeywordsThromboembolism Leiden mutation Next generation sequencer
Because the causes of venous thromboembolisms (VTEs) are various, it is important to differentiate inherited thrombophilia. The coagulation factor V R506Q (FV Leiden) mutation, which is known to be a cause of VTE, is often seen in Caucasians, whereas the mutation has not been reported in the Japanese population [1, 2]. We present the first case of VTE caused by coagulation FV Leiden mutation in Japan, demonstrating the usefulness of next generation sequencing (NGS).
The patient gave his consent for the publication of this study.
Discussion and conclusions
Recently, DVT has been focused on and recognized by medical professionals and by general citizens. In general citizens, long flight thrombosis, so-called “economy class syndrome”, and VTEs caused by sleeping in a vehicle after a disaster  have been reported by mass media. In medical professionals, mechanical compressions , malignant diseases [7, 8], lower limb operations , sedentary postures for long periods and central vein catheters cause VTEs, and DVT often results in fatal pulmonary thromboembolism. Generally, as globalization has advanced in Japan, flexibility in diagnosis and treatment is becoming increasingly necessary.
In 1993, Dahlbäck and colleagues reported familial thrombophilia due to a resistance to activated protein C . This abnormality is caused by the substitution of a single amino acid—glutamine for arginine—at position 506 (arginine506 → glutamine) in the coagulation factor V molecule . This mutated factor is also referred to as FV Leiden (R506Q), which is named after a city in the Netherlands that has many family lineages . This mutation is found in approximately one fifth of patients with venous thromboembolism in western countries , and it has a much stronger association with DVT than with VTE; this observation is called the Leiden paradox . The risk of recurrent thromboembolic events is significantly higher in carriers of FV Leiden than in patients without this abnormality ; however, FV Leiden is not reported to be a strong predictor of recurrent VTE .
In this case, the patient was young and healthy, had no past history and was not taking any regular medications. In addition, the trauma in right lower extremity was relatively mild. Therefore, the occurrence of VTE was thought to be triggered by a trauma in addition to genetic background. DOAC is effective for the treatment of VTE, in addition to the prevention of brain infarction in atrial fibrillation . Some recent reports demonstrated that direct thrombin inhibitors (dabigatran, argatroban, and bivalirudin)  and a DOAC (rivaroxaban)  are effective for VTE caused by FV Leiden; this case revealed apixaban was also effective.
NGS has revolutionized genetic research and the molecular diagnosis of human genetic disease . Targeted gene panel sequencing provides enhanced sequencing depth and can avoid incidental findings while being cost-effective compared with sequencing the exome . In this case, our customized panel targeting congenital coagulation defects enabled the rapid detection of the causative gene mutation, which has not been identified in the Japanese population with high accuracy. Therefore, the technology may be useful for the clinical diagnosis of patients with suspected congenital coagulation defects without regard to race, which could facilitate effective diagnosis.
To the best of our knowledge, this case represents the first report of a VTE caused by FV Leiden in Japan. The present report suggests that all medical professionals in Japan should be aware of the presence of this mutation.
Direct oral anticoagulant
Deep vein thrombosis
Coagulation factor V
Next generation sequencing
We thank Takafumi Kobayashi, PhD from Illumina, Inc., Tokyo, Japan, for the excellent technical support in using the next generation sequencer.
We thank all of the paramedical staff and clinical secretaries for their kind support during this work.
Availability of data and materials
Please contact author for data requests.
All authors engaged in clinical practice. All authors read and approved the final manuscript.
The authors declare that they have no competing interests.
Consent for publication
The patient gave his consent for the publication of this study.
Ethics approval and consent to participate
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