{'fraction_non_alphanumeric': 0.02918531781557744, 'fraction_numerical': 0.017009847806624886, 'mean_word_length': 5.172375690607735, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Recurrent vital thrombotic events in a young man with FVIII gene duplication

To the Editor: The coagulation system is a complex regulatory system in the human body. In this case, the young patient had various vital thrombosis, including cerebral venous sinus thrombosis (CVST), coronary thrombosis, and left ventricular thrombus. However, the patient had neither hypercoagulable-related diseases nor risks nor coagulative or fibrinolytic protein deficiency. Further genetic testing did not show the usual gene mutations relevant to coagulation dysfunction. We report such a patient with a slight elevation in coagulation FVIII activity and a rare FVIII gene duplication.

The patient was a 24-year-old man with a history of CVST 3 years prior, and he was treated with warfarin (3 mg/day) for 1 year. Risk factors for atherosclerosis were initially absent, and he had no family history of coronary heart disease or recurrent thrombosis. The patient presented to the emergency room with intermittent chest pain for 11 days and oppressive ongoing chest pain for 11 h. The electrocardiogram showed ST-segment elevation in lead I, aVL, and V1-V6 [ Figure 1A].
His blood pressure was 145/78 mmHg, and his heart rate was 118 beats/min. No cardiac murmurs, crackles, or wheezes of lung bases were noted by auscultation.
Emergency coronary angiography revealed that the left anterior descending (LAD) artery was incompletely obstructed with a thrombus that progressed distally [ Figure 1C]. After thrombus aspiration therapy the coronary angiography showed LAD reperfusion [ Figure 1D]. Optical coherence tomography (OCT) was performed after thrombus aspiration. The artery wall appeared to be normal, and the 3-layered architecture was clearly visible [ Figure 1E and 1F] combined with a massive red thrombus [ Figure 1G]. His echocardiography showed the decreased motion of the left ventricular apex.
The patient was administered a continuous infusion of platelet IIb/IIIa inhibitor (tirofiban 0.125 μg·kg −1 ·min −1 ) for 24 h followed by low-molecular-weight heparin (Clexane 6000 U every 12 h) for 4 days. His chest pain was relieved and the electrocardiogram showed ST-segment resolution [ Figure 1B]. Based on secondary prevention, the patient was treated with dual antiplatelet drugs, an angiotensinconverting enzyme inhibitor (ACEI), a b receptor blocker, and statin; folate was added because of hyperhomocysteinemia. Anticoagulant therapy was not included given that no evidence of hypercoagulability was found.
Four weeks after the MI, echocardiography showed left ventricular mural thrombus without any left ventricular wall motion abnormalities. The patient was then treated with warfarin (3 mg/day) in addition to dual antiplatelet therapy. Before warfarin was applied, his plasma levels of coagulation factor were assessed, with a slight elevation of coagulation FVIII activity to 166% (Normal range 100%-150%) noted; other coagulation factors were in the normal range. The hematological system panel test revealed a duplicate chrX: 153991029-154348425 region (including FVIII entire gene, GenBank: NM_000132.4). Two months later, echocardiography showed that the mural thrombus had disappeared. The patient was administered dual antiplatelet and warfarin therapy for 6 months, followed by aspirin and warfarin for 5 months. No recurrent thrombosis occurred.
The patient had been diagnosed with CVST at the age of 21 years. CVST is a potentially devastating, though rare, thrombotic event, with an annual incidence of 3 to 4 cases per million individuals. [2] CVST occurs most often in young women, especially during pregnancy and the puerperium period, or in other acquired and congenital prothrombotic conditions such as infection. [3] The European Stroke Organization guidelines recommend using oral anticoagulants for 3 to 12 months after CVST.
FVIII is a glycoprotein that plays a crucial role in the intrinsic pathway of blood coagulation. Elevations in FVIII levels are thought to be an independent risk factor for venous thrombosis. Elevated FVIII occurs frequently in patients with CVST and is a strong risk factor for this condition. [4] The relative contributions from genetic and inherited factors in the etiology of persistently elevated plasma FVIII levels remain unknown. Nevertheless, inherited factors may be important in at least some patients. [5] It remains unknown what gene mutations lead to FVIII elevation. Regarding the present case, the FVIII gene region duplication currently available in the Database of Genomic Variants does not cover the region we identified. Such changes might alter the production, activity, or metabolism of FVIII, affecting hemostasis and coagulation. Nonetheless, further mechanistic research is needed. Recent research found that JAK2 V617Fpositive essential thrombocythemia patients complicated with CVST were more likely to having thrombosis. [6] Therefore, genetic tests may contribute to risk stratification in CVST patients. This is a rare report of a patient who had a coronary thrombosis combined with CVST. Coagulopathy should be taken seriously, and genetic studies may be helpful.

Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/ have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.