The risk of thrombotic complication is high in patients with malignant tumor, and this condition is referred to as Trousseau syndrome [
3]. Varki reported multiple mechanisms of hypercoagulability in patients with malignant tumor, involving tissue factor, mucin, cysteine protease, and various cytokines [
4]. Especially, mucin promotes platelet aggregation by interaction with platelet P-selectin and leukocyte L-selectin, with resulting hypercoagulability [
5]. CA125 is a repeating peptide epitope of mucin MUC16 and a marker of mucin-producing malignant tumors such as ovarian cancer [
6]. Elevation of CA125 in patients with a malignant tumor increases the risk of ischemic stroke [
7‐
9]. Hypercoagulability and elevation of CA125 in patients with adenomyosis has also been reported [
1,
2], and as for patients with cancer, hypercoagulability can occur in patients with adenomyosis due to increased expression of tissue factor [
2]. Indeed, as shown in Table
1, elevation of D-dimer at onset has been found in all except one of the reported cases of ischemic stroke related to adenomyosis. Elevation of CA125 was also detected in both of our cases. The previous and current cases indicate that adenomyosis itself seems to cause hypercoagulability through a mechanism similar to that of Trousseau syndrome and may cause ischemic stroke. In contrast to previous reports, both of our patients had large vessel occlusion with emboli and large infarction. As for patients with Trousseau syndrome, both multiple infarction and large vessel occlusion can also occur in patients with mucin-producing adenomyosis and could cause severe neurological deficits, as shown in our cases.
Table 1
Summary of cases of ischemic stroke related to adenomyosis
| 45 | 159 | 1.1 | Antiplatelet, GnRH agonist | (−) |
| 44 | Not mentioned | FDP 5.9 μg/mL | Warfarin, GnRH agonist | (−) |
| 55 | 42.6 | 0.57 (normal) | Aspirin, GnRH agonist | (−) |
| 42 | 1750 | 6.0 | Antiplatelet (6 m). GnRH agonist (6 m) | (+) |
| 42 | 907 | 4.1 | Warfarin, GnRH agonist | (−) |
| 59 | 334.8 | 7.0 | Discontinuation of hormone replacement therapy | (−) |
7b | 42 | 395 | 1.4 | Warfarin | (−) |
8b | 50 | 143 | 3.7 | Rivaroxaban | (−) |
The primary approach to treatment of Trousseau syndrome is to eliminate the causative tumor. This approach could be used for patients with cerebral infarction associated with adenomyosis, but the benign characteristics of the lesion and limited evidence for the cause make it hard to choose surgery as first-line treatment. A gonadotropin-releasing hormone (GnRH) agonist may be a treatment option, based on its effect of decreasing secretion of estrogen. However, side effects restrict the administration period of a GnRH agonist, and there is a report of a patient (Case No. 4 in Table
1) who had recurrent ischemic stroke after discontinuation of a GnRH agonist [
8,
9]. Antithrombotic drugs are another treatment option. In patients with Trousseau syndrome, heparin, warfarin and other direct oral anticoagulants have been used to prevent thrombosis, although it is still unclear which drug is the most effective [
10]. Anticoagulants and antiplatelet agents can also be used in patients with adenomyosis. In our patients, warfarin and rivaroxaban were administered and there have been no recurrent attacks. Long-term hormone replacement therapy may cause hypercoagulability in patients with adenomyosis, and discontinuation of this therapy in one reported case (Case No. 6, Table
1) did not lead to recurrence [
11]. Overall, further studies are needed to clarify the mechanisms of development of cerebral infarction in patients with adenomyosis or other mucin-producing benign.