On 15 June 1341, Andronikos III died. He was succeeded by their son John V who was still three days short of his ninth birthday. Anna was appointed regent for her son. However Andronikos III had entrusted the administration to his advisor John Kantakouzenos. Anna did not trust the powerful advisor. At about the same time, Stefan Uroš IV Dušan of Serbia launched an invasion of Northern Thrace. Kantakouzenos left Constantinople to try to restore order to the area. In his absence, Patriarch John XIV of Constantinople and courtier Alexios Apokaukos convinced Anna that the senior advisor was her enemy. Anna declared Kantakouzenos an enemy of the state and offered the title of eparch of Constantinople to Apokaukos. Kantakouzenos was still in control of part of the Byzantine army. On 26 October 1341, he answered by proclaiming himself emperor at Didymoteicho. This was the beginning of a civil war that would last until 1347. Ivan Alexander of Bulgaria soon allied with the faction under John V and Anna while Stefan Uroš IV Dušan of Serbia sided with John VI. Both rulers were actually taking advantage of the civil war for their own political and territorial gains. In time John VI would ally himself with Orhan I of the nascent Ottoman emirate. At the same time Anna was attempting to gain support from Western Europe. In Summer, 1343 an emissary proclaimed her loyalty to Pope Clement VI in Avignon. In August, 1343, Anna pawned the Byzantine crown jewels to the Republic of Venice for 30,000 ducats as part of an attempt to secure more finances for the war. However Anna at last lost the war. On 3 February 1347, the two sides reached an agreement. John VI was accepted as senior emperor with John V as his junior co-ruler. The agreement included the marriage of John V to Helena Kantakouzene, a daughter of John VI. John VI entered Constantinople and took effective control of the city.
Later years
In 1351, Anna left Constantinople for Thessaloniki. She held her own court in the city, issuing decrees in her name and even controlling a mint. She was the second Byzantine empress to hold court in Thessaloniki, following Irene of Montferrat. Her rule there lasted to about 1365. Her last official act was the donation of a convent in the memory of Agioi Anargyroi. Agioi Anargyroi is the joined description of Saints Cosmas and Damian, who supposedly offered free medical services. Their devotees usually pray for healing. The donation may indicate Anna suffering from poor health and hoping for a cure. A little later she became a nun and died under the name "Anastasia" ca. 1365.
