Acquired Thrombophilia in Patients on Hemodialysis with Recurrent Vascular Access Thrombosis

Acquired Thrombophilia in Patients on Hemodialysis with Recurrent Vascular Access Thrombosis

R. Klamroth, O. Eike, F. Seibt, S. Gottstein, H. Rimpler and H. Landgraf

Introduction

Vascular access site thrombosis in patients receiving hemodialysis is a major cause of hospital admission and recurrent surgery [2]. The underlying pathologic cause is often stenosis of the venous vessel due to fibromuscular hyperplasia [5]. But in the case of early failure occasional studies have investigated that hypercoagulability could play an important role in this context [6]. The presence of antiphospholipid antibodies seems to be correlated with increased risk for thrombotic complications of vascular hemodialysis access [9].

Aim of the Study

Is there a higher prevalence of hereditary and acquired thrombophilic risk factors in patients with vascular access thrombosis in comparison to patients vascular access thrombosis?

Patients

In 2002 we examined 40 consecutive patients receiving hemodialysis. 22 patients had a history of vascular access site thrombosis (group 1) and 18 patients had not and a vascular access for longer than one year (group 2). All patients in group 1 had a history of at least two occlusions of vascular access. All 10 patients with prosthetic

I. Scharrer/W. Schramm (Ed.)

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Hemophilia Symposium Hamburg 2003

” Springer Medizin Verlag Heidelberg 2005

Table 1. Patients

All patients Group 1 Group 2

n 40 22 18

Age (years) 65,8 64,4 67,6

Women/men 20/20 11/11 9/9

Vascular access thrombosis 22 22 0

Arteriovenous fistula 30 12 18

PTFE prosthetic graft 10 10 0

grafts in group 1 had a history of thrombosis of arteriovenous fistula before implantation of PFTE graft. Patients with known systemic lupus erythematodes were excluded.

Methods

In every patient hereditary and acquired thrombophilic risk factors were deter- mined including antithrombin, protein C, protein S, factor V-G1691A-mutation, prothrombin-G20210A-mutation, homocysteine, lipoproteine (a), lupus anticoagu- lant, cardiolipin antibodies IgG and IgM , fibrinogen and factor VIII.

Platelet hyperreactivity was studied by light transmittance aggregometry in platelet rich plasma (Aggregometer PAP 4, Fa. Mölab). Aggregation was recorded as the maximum percentage change in light transmittance from baseline using platelet poor plasma as a reference. We defined »sticky platelets« as platelet aggre- gation > 30% after induction with different concentrations of ADP (10, 1 and 0,5 µmol) in platelet rich plasma [8].

Results

The results of thrombophilia evaluation are presented in the in Table 2. We found in 50% of patients with vascular access site thrombosis antiphospholipid antibodies in comparison to only 12% in patients without thrombosis. The patients in group 1 showed more activated platelets than patients in group 2. There were no significant differences in the number of hereditary risk factors in both groups.

270 R. Klamroth et al.

Table 2. Thrombophilic risk factors

Group 1 (n=22) Group 2 (n=18)

Lupus anticoagulant positive 11/22 2/18

Cardiolipin antibodies IgG positive 6/22 0/18

Sticky platelets syndrome 9/22 3/18

Homocysteine (< 15 µmol/l) 31,6 ± 21 µmol/l 21,8 ± 10 µmol/l

Fibrinogen (1,8 -3,5 g/l) 4,3 ± 1,0 g/l 4,9 ± 1,4 g/l

Factor VIII (80-150%) 224 ± 100% 213 ± 44%

Factor V-G1691A-mutation 2/22 1/22

Lipoprotein (a) (< 300 mg/l) 286 ± 301 mg/l 286 ± 219 mg/l

Antithrombin (80 – 150%) 102 ± 13% 106 ± 19%

Protein C (70 – 150%) 101 ± 17% 96 ± 28%

Protein S (70- 140%) 94 ± 27% 91 ± 21%

Prothrombin-G20210A-mutation 0/22 0/22

Discussion

We found in all 40 patients thrombophilic risk factors like elevated factor VIII, homocysteine and fibrinogen concentrations. The higher concentrations of homo- cysteine are due to end stage renal disease. One possible cause for higher concen- trations of fibrinogen and factor VIII, activated platelets and antiphospholipid anti- bodies could be a chronic inflammational process in patients receiving hemo- dialysis [4].

In the etiology of recurrent vascular access thrombosis only higher platelet activation and antiphospholipid antibodies play an important role [3, 7]. The influ- ence of homocysteine levels on vascular access thrombosis remains controversial [2, 10]. We found slightly higher concentrations of homocysteine in patients with thrombotic complications of vascular access. The hereditary thrombophilic risk fac- tors in comparison to the acquired factors were less important. In our small group we could not find any relevant differences.

Conclusions

In patients receiving hemodialysis we found a high prevalence of acquired throm- bophilic risk factors. There seems to be causal relation between vascular access site thrombosis and especially antiphospholipid antibodies and activated platelets. The evaluation of thrombophilic risk factors in patients with recurrent vascular access site thrombosis could lead to an improved antithrombotic therapy.

References

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