The writing seems smaller than previous samples, with a middle-zone lacking his trademark strength and confidence. The signature is also striking. Both the christian name and surname have reverse crossings out. Usually, Hemingway starts his signature crossings-out from the 'H' in reverse direction, crosses the 't' and ends through the Greek 'E' of his christian name. In this case, the one long line becomes two. Crossings-out in a signature are symbolic of self-destruction (but this is just one sign and should not be taken out of context to infer meaning on its own). The spacing seems pretty good though, pointing to clarity of thought, despite the unsteady progression of the script.
When this letter was written, Hemingway's physical and mental health had been in slow decline, following a series of terrible accidents, including two plane crashes on the same day in 1954. As a result, he lost all kidney function, leading to high blood pressure. This necessitated the use of medical drugs which lead to the side effect of depression. In 1960, he started to undergo a series of electro-shock treatments over the course of the next year or so. This destroyed his memory, leading to further despair. He would beg his wife on his knees not to send him back for more treatment.
Hemingway committed suicide on July 2 1961 at his home in Idaho, a day after his 36th shock treatment. There has been five suicides in the Hemingway family over four generations, including two of Hemingway's siblings. A tragic end to the life of one of the 20th Century's great novelists.