Association between platelet-related hemostasis impairment and functional iron deficiency in hemodialysis patients.

Hemostasis impairment and iron deficiency are relatively frequent in hemodialysis patients. Both conditions may contribute to anemia. The aim of our study was to explore possible associations between hemostasis impairment and iron deficiency by employing recently introduced methods for measurement of both conditions. Sixty-three hemodialysis patients were studied, with 30 age-matched, healthy controls. Hemostasis impairment was detected by in vitro closure time tests (collagen/epinephrine cartridge: CEPI; collagen/adenosine diphosphate (ADP) cartridge: CADP), whereas (functional) iron deficiency was measured by reticulocyte hemoglobin content (CHr) and the percentage of hypochromic red cells (HRC). We found that the patient group (N=14) with functional iron deficiency (CHr<29) had significantly delayed in vitro closure times in comparison to the patients (N=49) without functional iron deficiency. Furthermore, both types of closure time (CEPI and CADP) correlate highly significantly with CHr (P=0.002, and P=0.001). Such an association was not observed between in vitro closure time and HRC. We found a significant correlation between hemostasis impairment (measured by in vitro closure time) and iron deficiency (measured by CHr) in hemodialysis patients. This correlation has not previously been reported. It seems that in hemodialysis patients the hemostasis impairment affects (functional) iron deficiency, most likely by facilitating excessive blood loss and consequent iron deficiency. Thus, it appears that a delayed in vitro closure time along with decreased CHr may identify hemodialysis patients who suffer (occult) blood loss and/or excessive blood loss during hemodialysis procedure. The clinical value of this finding should be tested in larger studies.

The study of anaemia-related haemostasis impairment in haemodialysis patients by in vitro closure time test.

It is known that anaemia in haemodialysis patients could contribute to haemostasis impairment. However, the precise relation between the degree of anaemia and the degree of haemostasis impairment is not known, nor the optimal level of hematocrit above which anaemia no longer disturbs haemostasis. Our study addresses these clinically relevant questions by employing in vitro closure time test, a new method in which the process of platelet adhesion and aggregation following vascular injury is simulated in vitro in samples of whole blood. We studied 63 haemodialysis patients, with 30 age-matched, healthy controls. Results show that patients with hematocrit below 0.32 (N=28) had significantly impaired primary haemostasis, in contrast to patients with hematocrit above 0.32 (N=35), as measured by both types of closure time test. A significant negative association was found between hematocrit values and closure time (CEPI cartridges: rho=-0.41, p<0.001; CADP cartridges: rho=-0.47, p<0.001). A multiple logistic regression model for predicting prolonged closure time confirmed this finding. Nonparametric curve fitting enabled estimation of the level of hematocrit at which the values of in vitro closure time in haemodialysis patients do not differ from those in the controls at approximately 0.35. ROC analysis confirmed this to be the optimal threshold for predicting prolonged closure time for both cartridges. By using in vitro closure time test, we confirmed that anaemia correlates with the severity of haemostasis impairment. We estimated the target level of hematocrit above which anaemia no longer affects haemostasis to be about 0.35. These new results (and new assay) appear to have clinical value for treating haemodialysis patients.

The effect of long-term, low-dose tranexamic acid treatment on platelet dysfunction and haemoglobin levels in haemodialysis patients.

Some previous studies suggest that activation of the fibrinolytic system may induce platelet dysfunction in haemodialysis patients. Accordingly, inhibition of fibrinolysis may improve platelet dysfunction, and speculatively increase haemoglobin levels. We tested this hypothesis. The study group comprised 22 patients (14 male, 8 female, median age 62), who had been on maintenance haemodialysis for more than one year. Patients were treated for three months with low-dose tranexamic acid (TXA), a potent anti-fibrinolytic agent. The dosages of erythropoietin and the haemodialysis procedure were not changed significantly during the study. We primarily followed platelet function (by in vitro closure time test) and haemoglobin values. Patients were divided into those with substantially prolonged (N = 9) and those with slightly delayed or normal (N = 13) in vitro closure time. Treatment with TXA resulted in a significant improvement of platelet function and increased levels of haemoglobin in the first group, and no changes in either platelet function or haemoglobin values in the second group. TXA in the dosage used was biologically active, since a significant decrease in plasminogen and D-dimer were found in both groups. No significant changes in other fibrinolytic parameters or von Willebrand factor were found. No complications in terms of arterial or venous thrombosis were observed. Our pilot study suggests that long-term, low-dose TXA treatment of haemodialysis patients with substantially prolonged in vitro closure time results in a significant improvement of platelet dysfunction and a significant increase in haemoglobin values. These new, promising results merit further investigation in larger studies.

Tranexamic acid is beneficial as adjunctive therapy in treating major upper gastrointestinal bleeding in dialysis patients.

BACKGROUND: In a pilot, non-randomized trial we tested the efficacy of tranexamic acid (TXA), a potent fibrinolytic inhibitor, as adjunctive therapy in standard treatment of major upper gastrointestinal bleeding in dialysis patients. METHODS: Twenty consecutive patients (12 male, eight female; 63+/-8 years) with 36 episodes of major upper gastrointestinal bleeding were included in the study. In 16 episodes of bleeding TXA was used (in a dosage of 20 mg intravenously, followed for the next 4 weeks by 10 mg/kg/48 h orally), whereas in 20 other cases of bleeding, TXA was not used. The decision to use TXA was left to the attending physician's clinical judgement, resulting in all the more severe cases of bleeding being treated with TXA. RESULTS: Treatment including TXA was shown to be beneficial (relative to cases not treated with TXA) in terms of decreasing the rate of early re-bleeding (in the first week, 0 vs 6, P<0.05), the rate of early and late re-bleeding (in the first month, 1 vs 8, P<0.05), the rate of repeated endoscopic procedures (in the first month, 1 vs 8, P<0.05) and the number of blood transfusions needed (in the first month, 1.4+/-1.3 vs 2.6+/-1.5 units, P<0.05). CONCLUSIONS: The results of this pilot study suggest that TXA can be beneficial in the treatment of major upper gastrointestinal bleeding in dialysis patients. This remains to be definitely confirmed in a randomized study.