Protein Z Deficiency in Patients with Bleeding History. Is It a Coagulopathy?.

Protein Z (PZ) is a vitamin K-dependent protein. In hemostasis PZ has two functions: together with Factor Xa it forms an inhibiting complex with the PZ- dependent protease-inhibitor and it enhances binding of Thrombin to phospholipid surfaces. Therefore, low PZ levels may induce thrombosis or bleeding.

The latter has been questioned by Vasse 2008 and in 1995 Kemkes-Matthes reported in 58% of patients (pts) with a bleeding history PZ deficiency as the only abnormality.

To evaluate if low PZ levels are associated with a bleeding tendency, we reviewed data of pts referred to or laboratory. PZ determination is part of our diagnostic work up, including whole blood count, PT, PTT, VWF/FVIII-complex, FXIII and platelet function studies.

Over a 1 year period we investigated PZ level in 173 pts. PZ concentration was determined by ELISA (Asserachrom Protein Z; Diagnostica Stago), a sandwich immunoassay using a mouse monoclonal antibody against PZ, normal range 1600 – 3300 μg/l, mean 2600 μg/l published by Miletich. Our normal range obtained by 62 donors 990–2490, mean 1740μg/l (+/− 2SD). PZ <1000μg/l is considered to be abnormal.

In 75/173 (43%) pts with a bleeding history (e.g. postoperative hemorrhage, epistaxis, menorrhagia) no coagulation abnormality was detected. In 41/98 (42%) low PZ level was the only abnormality (mean PZ 642, range 195–994). 57/98 (58%) were diagnosed with vWD n=17; platelet function disorders n=10 or ASA/drugs causing platelet dysfunction n=20, others n=10. In 21/57 (37%) low PZ level was detected additionally (mean PZ 699μg/l; range 219–949) and in the remaining 36/57 (mean PZ 1689; range 1036–2842).

Surprisingly, in 24% of pts with a bleeding history the only abnormality was PZ deficiency. Therefore, we consider PZ determination a useful parameter in patients with a bleeding history after ruling out more common disorders. Low PZ levels may cause a coagulopathy in some pts.

No relevant conflicts of interest to declare.