After completing his studies, he practiced medicine in Peine for four years, and in 1725 moved to Hannover, where he became one of the more influential physicians in Europe.
In 1735, Werlhof coined the name "morbus haemorrhagicus maculosus" which was later referred to as idiopathic thrombocytopenic purpura (ITP), a bleeding disorder.
However, his description of the condition is not in keeping with ITP: He wrote: "Vidi, verbi causa, ante quinquennium, ubi solitarius hic affectus, in puella decenni, haemorrhagiam largam sanguinis foetidi, sinceri partim, partim nigri, partim serosi, per nares, gingivas, arteriam asperam, vomitum, fecessium, urinam, a primo inde initio ad finem usque, alternis ανωμαλως vicibus, produxit, cum animi deliquiis et extremorum perfrigeratione, et maculis totum sensim corpore erumpentibus, copiosis, nigerimis."
This description is more compatible with a generalized coagulation disorder (DISQUISITIO MEDICA ET PHILOLOGICA DE VARIOLIS ET ANTHRACIBUS - PAUL GOTTLIEB WERLHOF, 1735, page 79).
Among his written works were a 1732 treatise on fevers called Observationes de febribus, and a collection of poetry titled Gedichte.