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Long term follow up of von Willebrand factor and plasminogen activator inhibitor-1 in patients with polymyalgia rheumatica
  1. AGNETA UDDHAMMAR,
  2. SOLBRITT RANTAPÄÄ-DAHLQVIST
  1. Department of Rheumatology
  2. Department of Clinical Chemistry, University Hospital of Northern Sweden, S-901 85 Umeå, Sweden
  1. Dr A Uddhammar.
  1. TORBJÖRN K NILSSON
  1. Department of Rheumatology
  2. Department of Clinical Chemistry, University Hospital of Northern Sweden, S-901 85 Umeå, Sweden
  1. Dr A Uddhammar.

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In polymyalgia rheumatica (PMR) subclinical vasculitis is suggested in the pathogenesis of the disease.1 2 Von Willebrand factor (vWF), produced by endothelium and megakaryocytes, is an important haemostatic factor.3In healthy people with ABO blood group O, vWF values are lower than in people with a blood group other than O.4 Increased plasma concentrations of vWF indicate endothelial damage5 and are found in diseases that involve blood vessels5 6 including vasculitis.7 In PMR and giant cell arteritis high vWF concentrations persist after acute phase proteins are normalised,8 9 but a gradual decline over time is also reported.10 11 Plasminogen activator inhibitor-1 (PAI-1) is an inhibitor of tissue plasminogen activator and is released from endothelial cells.12 Decreased fibrinolysis because of increased plasma concentrations of PAI-1 is associated with vasculitis in rheumatoid arthritis.7 Glucocorticoids induce PAI-1 synthesis13 and genetic variation affects individual concentrations.14

We studied the plasma concentrations of vWF and of PAI-1 in PMR patients over time as the inflammation receded. The potentially confounding impact of ABO blood group and of corticosteroid treatment on these values were also evaluated.

Thirty seven patients (25 women, 12 men), mean (SD) age 70 (8) years, with PMR (criteria of Bird et al 15) were prospectively followed up until 1996. Follow up blood samples were collected from 31 of the original 37 patients after a median time of 5.8 years (range 3.0–8.8). Five patients died during the observation period and no blood sample was available from one patient. For analysis of vWF and PAI-1, blood was collected in the morning. vWF and PAI-1 were measured as previously described.8

The plasma concentrations of vWF and PAI-1 increased significantly (p<0.05), while erythrocyte sedimentation rate (ESR), C reactive protein (CRP), fibrinogen and platelets decreased (p<0.0001) (table1). From the patients with paired samples (n=31) two patients with clinical and laboratory relapse of PMR and three who had developed diabetes mellitus were excluded. In one patient information of the blood group was not available. Among the remaining patients, those with blood group non-O (n=16) showed high vWF values, median 197%, which rose to 230% (p<0.05) (fig 1), whereas those with blood group O (n=9), showed no increase in vWF, median 160% and 166%, respectively. At follow up non-O patients had higher vWF concentrations than blood group O patients (p<0.05) (fig 1). The blood groups were unrelated to PAI-1 values.

Table 1

Laboratory data in 31 patients with PMR at diagnosis and at follow up after a median time of 5.8 years. Data are presented as medians and (interquartile range) and were analysed using Wilcoxon signed rank test

Figure 1

Plasma concentrations of vWF in 25 patients with PMR at diagnosis and at follow up subgrouped according to ABO blood group O (open boxes) and non-O (filled boxes). Data are presented with 10th, 25th, 50th, 75th, and 90th percentiles. Wilcoxon signed rank test was used for paired data and Mann-Whitney U test for unpaired data.

The concentrations of vWF at follow up did not differ between patients receiving prednisolone treatment, mean (SD) dose 3.0 (1.5) mg, (n=10), median 227% (interquartile range 166–246), and those who were clinically inactive and not receiving treatment (n=16), median 190% (137–238). PAI-1 increased significantly in patients taking prednisolone, from median 8.9 IU/ml (6.7–11.6) at diagnosis to 11.6 IU/ml (9.4–25.3) at follow up (p<0.05), but not in patients who had completed their treatment, median 11.2 IU/ml (6.4–17.0) to 11.8 IU/ml (8.6–13.8) at follow up.

In patients with non-O blood groups there was a correlation (Spearman rank test) between vWF and ESR, CRP, fibrinogen, and age at disease onset (r s=0.61,r s=0.62, r s=0.63,r s=0.79, p<0.01, p<0.05, p<0.01, p<0.001 respectively), but not in patients with blood group O. PAI-1 correlated with CRP (r s=0.39, p<0.05) in all patients at diagnosis. There were no differences in ESR, CRP, fibrinogen or platelet count between patients with and without blood group O.

From these results we conclude that even in an inflammatory disease such as PMR, the ABO blood group and age influence the magnitude of the vWF concentrations and may explain the contradictions pertaining to vWF values reported in inflammatory diseases. In agreement with our earlier study8 PAI-1 values were increased in PMR patients after several years of prednisolone treatment. Persistently high concentrations of vWF about six years after PMR diagnosis, suggest a continuous vascular dysfunction despite clinical and laboratory determined remission.

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