Protein z Deficiency in Risk Pregnant Women

The regulation of blood coagulation takes place in the complex interaction between procoagulatory, inhibitory and thrombolytic factors. The glycoprotein protein Z belongs to these coagulation regulators and is formed in the liver. In contrast to most other coagulation factors, Protein Z itself has no enzyme activity, but is an important cofactor for other coagulation-active plasma proteins. One of these plasma proteins is the protein Z-dependent protease inhibitor (ZPI), which together with calcium and components of the cell surface forms a complex that inactivates the activated coagulation factor Xa required for clot formation, comparable to the oral Xa antagonists Rivaroxaban, Apixaban or Endoxaban.

Protein Z accelerates this process about1000-fold and leads primarily to an inhibition of blood coagulation due to the inactivation of factor Xa. The consequence of a protein Z deficiency is therefore a tendency to thrombosis. Similar to ZPI on factor Xa, heparin acts as a catalyst on antithrombin and this inhibits blood coagulation. There is also evidence that another coagulation factor, thrombin, which is activated by factor Xa, is only bound to cell surfaces (especially thrombocytes) in the presence of protein Z. This binding is necessary to prevent thrombin from diffusing away and the associated rapid inactivation. It is discussed that protein Z also has a further coagulation-promoting effect via this mechanism. A deficiency can therefore lead to bleeding of the mucous membrane.

In the case of a protein Z deficiency, the risk of an early birth is increased by a factor of 3. Since May 2011, the plasma concentration of protein Z has been measured in 3825 patients at the Hemostaseologicum Berlin as part of the general coagulation status. In 1187 patients (31%) a protein Z deficiency was found. 688 had a slight protein Z deficiency with concentrations between 1000 and 1,500µg/l. 499 had a severe protein Z deficiency with concentrations below 1,000µg/l. Of these, 3009 had early, late laboratory or death births in prehistory.The slight protein Z deficiency all reached the reference range up to the 15th SSW. 220 patients with severe protein Z deficiency did not reach the reference range during the entire pregnancy. 44% reached the reference range in the 2nd trimester, 12% only in the last trimester. All patients with protein Z deficiency and miscarriages were treated with low molecular weight heparin, mostly tinzaparin.

Of these, 1128 gave birth to a healthy child, the others had abortions.