Plasma Protein Z Research Articles

Protein Z Levels Could Help To Predict Obstetrical Complications and Arterial Thrombosis in Patients with Antiphospholipid Antibodies.

Introduction: Protein Z (PZ) is a vitamin K dependant plasma protein synthesized by the liver. The precise physiological function of PZ is still unclear: - anticoagulant, the PZ-dependant protease inhibitor complex inhibits factor Xa and acts as a naturally occurring anticoagulant; - procoagulant, PZ promote the assembly of thrombin with PL vesicles- and promote coagulation. In clinical situations, low PZ plasma levels have been associated with bleeding and thrombotic tendency while elevated PZ plasma levels have been linked with ischemic stroke. Antiphospholipid syndrome (APS) is a complex autoimmune thrombotic disorder. Despite specific clinical and laboratory criteria, diagnostic and prognostic tools in patients with APS are limited in their ability to predict adverse outcome in patients with antiphospholipid antibodies (aPLA). Therefore, we hypothesized that PZ could play a role in the thrombotic tendency.Study: to evaluate our hypothesis, we measured PZ plasma concentrations in a case control study including 61 patients with confirmed aPLA with or without APS versus 53 controls. Among the group of patients with APS, 15 had obstetrical complications (OC), 16 had arterial thrombosis (AT) and 11 venous thrombosis (VT). Nineteen patients had aPLA without APS defining the APS(−) group. Plasma PZ antigen concentrations were measured on citrated plasma using the commercial ELISA kit, Asserachrom protein Z, (Diagnostica Stago).Results: PZ plasma levels were normally distributed. Normal PZ concentrations defined as mean ±2 SD were contained between 0.4 and 2.6 μg/mL. No difference was found in mean+ SD between male and female. Two per cents of controls and 18% of patients with venous thrombosis had PZ under 0.4 μg/mL. Forty per cents of patients with OC, 25% with AT and 18% with VT had PZ above 2.6 μg/mL. Plasma protein Z levels measured at least 6 month after any clinical event were significantly higher in APS patients than in controls and APS(−) patients [mean ± SD μg/mL, 2.0 ± 0.9 vs 1.5 ± 0.5 and 1.3 ± 0.5 respectively). According to the clinical complications, PZ concentrations were significantly greater in the group with OC (2.4+0.6 μg/mL) and AT (2.05+0.8 μg/mL) than in controls (1.5+0.5 μg/mL), VT(1.3+0.9 μg/mL) and APS(−) (1.3+0.5 μg/mL) patients [OC vs Controls: p<0.0001; AT vs Controls: p= 0.0047; OC vs AT: p= NS; OC vs APS(−):p< 0.0001; OC vs VT: p= 0.0016, APS(−) vs controls: NS; APS(−) vs VT: NS; VT vs Controls: NS; APS(−) vs AT: p=0.0034; AT vs VT: p= 0.05]. We found an increased relative risk of OC and AT with increasing PZ levels with odds ratios of 7.1 [95% CI: 2.1–23.7] for OC and 2.4 [95% CI: 1.1–5.4] for AT.Conclusion: our study retrospective on a small size sample, indicates that high protein Z plasma could be a high risk for obstetrical complications and a lower risk for arterial thrombosis in aPLA patients. Measure of PZ could help to evaluate obstetrical and thrombotic risk of patients with aPLA. Further prospective studies are needed to confirm our results.

Low protein Z levels in children with nephrotic syndrome

Acquired deficiency of anticoagulant proteins, due to loss in the urine, has been proposed as one of the major thrombogenic alterations in nephrotic syndrome (NS). Protein Z (PZ) is a single-chain vitamin K-dependent glycoprotein. Low PZ levels are reported to be a risk factor for thrombosis. The aim of this study was to investigate protein Z and other natural anticoagulant levels in children with NS. Thirty children aged between 1.5 and 12 years with NS (Groups I and II) and 19 age-and-sex-matched healthy controls (Group III) were enrolled into the study. Patients were divided into two groups: Group I (proteinuria >40 mg/m2/hr) and Group II (patients in remission). Plasma PZ levels in Group I were significantly lower than Group II (p=0.009) and group III (p=0.018). Plasma levels of AT III for Group I were significantly lower than for Groups II and III (p=0.009, p=0.005, respectively). Protein C levels in Group I were higher than in Group II and Group III (p=0.002, p=0.000, respectively). Protein Z levels positively correlated with serum total protein and albumin levels (p=0.003, p=0.003, respectively) and negatively with the degree of proteinuria (p=0.000). Protein Z levels were positively correlated with AT III (r=0.037, p=0.04). Along with the other coagulation abnormalities, decreased protein Z may contribute to increased risk of thromboembolic complications in children with NS. The negative correlation between proteinuria and PZ level suggests the possibility of renal PZ loss. Further studies are needed to investigate the mechanism and role of decreased PZ in NS.

Protein-Z-deficiency as a rare case of unexpected perioperative bleeding in a patient with spinal cord injury

Case report describing the management of repeated perioperative bleeding probably due to Protein-Z-deficiency in a post-traumatic paraplegic patient. To describe the difficulty in diagnosing this rare form of hypocoagulability and the monitoring and substitution concept during three elective surgical interventions. Spinal Cord Injury Center, Bergmannstrost, Halle, Germany. A 19-year-old male suffering from a post-traumatic paraplegia sub Th8 (ASIA-A) since childhood had experienced two life-threatening intraoperative bleeding incidents before finally Protein-Z-deficiency as the underlying coagulation disorder was diagnosed. After substitution of 2000 IE PPSB (Beriplex P/N) a repeatedly postponed implantation of a sphincter-externus (Brindley-) stimulator could be performed without bleeding complications, and this was also true for two additional urological interventions 1 year later. Protein-Z levels were monitored before, during and after the operations. The preoperative application of between 1000 and 2000 IE PPSB was safe and sufficient to raise the patients' plasma Protein-Z level to almost normal and so prevent excessive intraoperative blood loss. In case of repeated bleeding tendency of unknown origin it is mandatory to look for rare causes of hypocoagulability such as Protein-Z-deficiency. We developed a substitution concept using a plasma concentrate with guaranteed Protein-Z amount (PPSB) allowing the safe performance of elective surgical interventions.

A common polymorphism of the protein Z gene is associated with protein Z plasma levels and with risk of cerebral ischemia in the young.

The vitamin K-dependent protein Z (PZ) has been shown to possess anticoagulant as well as procoagulant properties. Plasma levels of PZ show a broad interindividual variation, but it is unknown to which extent this variation is under genetic control. Recent clinical studies revealed contradictory results on the association of PZ plasma levels and the risk of ischemic stroke. We performed a case-control study including 200 patients with cerebral ischemia aged < or =50 years and 199 control subjects from the same South German region. We investigated a possible association of 2 common single nucleotide mutations in the PZ gene with the risk of cerebral ischemia. Furthermore, enzyme-linked immunosorbent assay measurements were done in control subjects without vascular disease to detect a potential association of different genotypes with PZ plasma (antigen) levels. In patients, the frequency of the A allele of the intron F polymorphism G79A was significantly lower than in controls (15.7% versus 24.4%; odds ratio, 0.58; 95% CI, 0.39 to 0.86; P=0.007; adjusted for age, sex, and conventional risk factors). The G allele of the promoter polymorphism A-13G tended to be less common in patients (4.2% versus 7.0%; adjusted odds ratio, 0.56; 95% CI, 0.28 to 1.13; P=0.105). In 42 control subjects, the A allele of the intron F polymorphism was associated with lower PZ antigen levels (P=0.0032; Spearman correlation coefficient rs=-0.48). The A allele of an intron F polymorphism of the PZ gene appears to be a novel protective genetic marker for the risk of cerebral ischemia in young adults. In the context of juvenile stroke, high PZ plasma levels may represent a prothrombotic condition.