Elevated hepatocyte growth factor levels at the beginning of high-flux hemodialysis are due to heparin administration.

BACKGROUND: It has been reported that hemodialysis (HD) stimulates hepatocyte growth factor (HGF) release, but it is not clear if this stimulation is due to HD itself or to heparin used during HD. To clarify this issue, we undertook the present study. METHODS: We studied 18 HD patients using high-flux dialyzers, during a single 4-hr hemodialysis session (session A). The dialyzers were pre-rinse with normal saline without heparin, and HD was started with zero ultrafiltration and without anticoagulation. Anticoagulation was administered as IV injection (80 IU/kg of LMWH enoxaparin sodium) 10 min after the beginning of HD. HD was continued for 10 more minutes and then as prescribed. HGF serum levels were measured before the beginning of the HD session (sample t0) as well as 10 and 20 minutes after the beginning of the session (samples t10 and t20). In six more patients (controls), the same study was repeated but without the administration of LMWH during the first 20 min of HD initiation (session B). RESULTS: In comparison with t0, t10 HGF serum levels changed significantly in neither session A nor in session B. However, at t20, HGF levels increased significantly in session A compared with t0 (increment 666.3 +/- 211.0%, p < 0.0001) and t10 (increment 894.2 +/- 506.0%, p < 0.0001), but not in session B. No differences were found between sessions A and B at samples t0 and t10 (p = NS). HGF serum levels at t20 in session A were found to be higher compared with corresponding levels in session B (p < 0.0001). CONCLUSION: Elevated HGF serum levels at the beginning of high-flux HD session are due to LMWH administration.

The effect of two different doses comprising the simultaneous administration of intravenous B-complex vitamins and oral folic acid on serum homocysteine levels in hemodialysis patients.

BACKGROUND: Several regimens using different doses of folic acid (FA) alone or supplemented with B-complex vitamins (BCVs) have been tested for their ability to reduce total homocysteine (tHcy) serum levels in hemodialysis (HD) patients. In the present study, we assessed the effect of two different doses comprising the simultaneous administration of intravenous (IV) BCVs and an oral FA supplementation on serum tHCy levels in HD patients. PATIENTS-METHODS: In a cohort of 49 patients (31 male, 18 female) undergoing chronic HD treatment for a mean of 40.0+/-40.7 months, serum concentrations of tHcy, folate and vitamin-B12 (vB12) were determined at the end of three sequential periods as follows: 20 weeks without any BCV and/or FA supplementation (period A), 20 weeks with a dose comprising the simultaneous administration of IV BCVs and an oral supplementation of 5 mg of FA once a week (period B), and 20 weeks with a dose comprising the simultaneous administration of IV BCVs and an oral supplementation of 5 mg of FA thrice a week (period C). An IV dose of BCVs consisting of a 5 mL solution containing vitamin B1 (250 mg), vitamin B6 (250 mg) and vitamin B12 (1.5 mg) was administered at the end of hemodialysis. RESULTS: Mean serum tHcy levels were significantly higher at the end of period A relative to levels at the end of periods B and C (35.8+/-23 micromol/L vs. 22.0+/-17.6 and 15.0+/-4.5 micromol/L, respectively; p<0.000001). Mean serum folate levels and mean serum vB12 levels were significantly lower at the end of period A relative to levels at the end of periods B and C (p<0.000001). Mean serum tHcy levels were lowest at the end of period C (p<0.000001 in comparison to periods A and B), and 26 of the 49 HD patients (67.3%) possessed tHcy levels below 16 micromol/L. CONCLUSIONS: In HD patients, high doses consisting of the simultaneous administration of IV BCVs and an oral FA supplementation resulted in the efficient reduction of serum tHcy levels.

HCO3 increment in arterial line can reveal significant vascular access recirculation in high-flux hemodialysis: a preliminary report.

We report a new and simple way that can reveal the presence of vascular access recirculation (VAR) in patients undergoing hemodialysis (HD). Acid-base and blood gas parameters (pH, pO(2), pCO(2), and HCO(3)) were measured in blood samples drawn from an arterial fistula needle before the initiation of HD and from arterial and venous lines simultaneously 5 min later, in 31 patients (group A). Vascular access recirculation was measured using the glucose infusion test (GIT) immediately after the withdrawal of the 5-min samples. The same study was repeated in 30 patients in whom HD lines were reversed (group B). A comparison with baseline (predialysis) values of an analysis of the arterial line in group A at 5 min revealed that pCO(2) increased by 1.14+/-2.5 mmHg and HCO(3) by 0.6+/-0.6 mM/L (p<0.02 and p<0.00001, respectively). The corresponding pO(2) and pH values did not show significant differences. Glucose infusion test at 5 min (GITa) was -0.058+/-0.03%. A comparison with baseline (predialysis) values of an analysis of the arterial line in group B at 5 min revealed that pCO(2) increased by 7.7+/-3.5 mmHg and HCO(3) by 2.9+/-1.0 mM/L (p<0.000001 in each case). The pH level was significantly lower in comparison with baseline values (p<0.00001), while pO(2) did not show a significant difference. Glucose infusion test at 5 min (GITb) was 12.0+/-6.1% (p<0.000001 in comparison with GITa values). Clinically significant VAR was defined as HCO(3) increment >1.8 mM/L, based on the receiver-operating characteristics curve, which showed a threshold value of HCO(3) increment >1.8 mmol/L as a predictor of GIT recirculation. Five minutes after the initiation of high-flux HD with a 0 ultrafiltration rate, there is a small increment in arterial HCO(3) values relative to predialysis values. Clinically significant VAR is present when this increment is higher than 1.8 mM/L.

pO2 and pCO2 increment in post-dialyzer blood: the role of dialysate.

Blood returning from a dialyzer during hemodialysis has a higher pO2 and pCO2 content than blood entering the dialyzer, and this has been attributed to the dialysate. The present study investigates this phenomenon. Acid-base and blood-gas parameters (pH, pO2, pCO2 and HCO3) were measured in three groups of stable chronic hemodialysis patients (A, B, and C) undergoing high-flux hemodialysis. In group A (n = 15), "arterial" (a) and "venous" (v) samples were withdrawn simultaneously before dialysis (samples A0), 5 min after circulation of the blood with the dialysate in the by-pass mode (samples A5), and 5 min after high-flux hemodialysis at a zero ultrafiltration rate (samples A10). In group B (n = 11) (a) and (v) samples were withdrawn simultaneously before dialysis (samples B0), 5 min after isolated-ultrafiltration with closed dialysate ports ("isolated-closed" ultrafiltration) (samples B5), and 5 min after high-flux hemodialysis at a zero ultrafiltration rate (samples B10). In group C (n = 14), after an initial arterial blood sample withdrawal before hemodialysis (sample C0), high-flux hemodialysis at a zero ultrafiltration rate was initiated. Five minutes later, blood and dialysate samples were withdrawn simultaneously from the hemodialysis lines (samples C5). In all cases blood and dialysate (bicarbonate) flow rates were set at 0.300 and 0.700 L/min, respectively. FLX-18 hemodialyzers (membrane PEPA 1.8 m2) were used in this study. Analysis of variance revealed significant changes only in venous samples. A comparison of arterial and venous samples revealed no differences between groups A and B before the initiation of dialysis (A0a vs. A0v and B0a vs. B0v, P = NS). The pO2 content was higher in A5v samples than in A5a samples (83.5 +/- 11.2 vs. 88.8 +/- 14.0 mm Hg, P < 0.02), while the level of HCO(3) was higher in A5a samples than in A5v samples (20.8 +/- 2.0 vs. 20.4 +/- 1.8 mEq/L, P < 0.05). A10a samples possessed a higher pH and lower levels of pO2, pCO2, and HCO3 in comparison to A10v samples (P < 0.001 for all). Mean pO2 and pCO2 values in A5v and A10v samples increased by 6.3% and 12.1% and by 1.29% and 52% in comparison to corresponding values of A5a and A10a samples, respectively. The pO2 level was the only parameter that differed significantly between B5a and B5v samples (B5a = 84.6 +/- 10.1 vs. B5v = 98.0 +/- 12.6 mm Hg, P < 0.005). B10a samples possessed a higher pH and lower levels of pCO2, pO2, and HCO3 in comparison to B10v samples (P < 0.0005 for all comparisons). Mean pO2 and pCO2 values in B5v and B10v samples increased by 16.2% and 16.3% and by -0.29% and 64.8% in comparison to corresponding values of B5a and B10a samples, respectively. C5a samples possessed a higher pH and lower levels of pCO2, pO2, and HCO3 in comparison to C5v samples (P < 0.001 for all). Mean pO2 and pCO2 values in C5v samples were, respectively, 16.0% and 65.0% higher than corresponding values of C5a samples. These results indicate that blood returning from the dialyzer after 5 min of high-flux hemodialysis has a higher pO2 and pCO2 than blood entering the dialyzer, and that this difference is due to O2 and CO2 transfer from the dialysate space into the blood.

Non-invasive cardiologic findings in patients with malignant melanoma*.

Although malignant melanoma has a great propensity (38-50%) for cardiac involvement, as indicated by autopsy findings, cardiac metastases are rarely identified ante-mortem. The aim of this study was to record abnormal electrocardiographic and echocardiographic findings in patients with malignant melanoma. One hundred and eighty-five consecutive patients (male/female, 99/86; mean age, 59.6 years) with histologically proven malignant melanoma (American Joint Committee on Cancer stages II-IV), and with no known history of heart disease, were evaluated prospectively over a period of 11 years. The cardiologic findings considered were an unexpected delayed conduction of an electrical stimulus, recorded by high-resolution signal-averaged electrocardiogram (presence of ventricular late potentials), prolongation of the PR, QRS and QTc segments in a surface electrocardiogram, and abnormal Q waves. Echocardiographic findings comprised pericardial implantation/effusion or presence of intracavitary/intramyocardial metastases. Forty-one abnormal findings were recorded, pertaining to 38 of the 185 patients (19.5%). In particular, PR interval prolongation was found in eight patients (4.3%) and QTc interval prolongation in 11 (6%). Abnormal Q waves were recorded in five patients (2.7%). The filtered QRS interval was prolonged in seven patients (3.8%). Finally, echocardiographic examination showed discrete pericardial implantations and small to moderate pericardial effusion in six patients (3.2%) and intracavitary/intramyocardial metastases in four (2.1%). The median survival of these patients was 33 months (95% confidence interval, 19.9-46.1 months). It can be concluded that abnormal electrocardiographic and echocardiographic findings are recorded at the time of diagnosis of the disease in a significant percentage of patients with malignant melanoma.

Therapeutic plasma exchange in patients with grade 2-3 hematopoietic stem cell transplantation-associated thrombotic thrombocytopenic purpura: a ten-year experience.

In the present retrospective study we report our 10-year experience with therapeutic plasma exchange (TPE) in 18 patients with grade 2-3 hematopoietic stem cell transplantation (HSCT)-associated thrombotic thrombocytopenic purpura (TTP). During TPE a mean total quantity of 26.5 +/- 15.1 L of plasma was exchanged. Five patients (27.7%) had a complete response eight patients (44.4%) had a partial response while five patients (27.7%) died during TPE treatment. Among the survivors, relapse of TTP occured in three patients (23%) and although these patients were treated again with TPE, all died. First-year survival rate was 41.2%. Our results indicate that TPE may be effective in the treatment of some patients with grade 2-3 HSCT-associated TTP.

Heparin solution locked in acute hemodialysis catheters: impact on activated partial thromboplastin time.

Fifteen patients on hemodialysis, wearing acute dual lumen hemodialysis catheters (DLHCs) locked with a 4 ml heparin solution (HS) containing 7,500 IU of conventional heparin (3,750 IU/lumen), were studied. After the preexisting HS was aspirated and discarded, 10 ml of blood was withdrawn from each lumen in a syringe. Then, two 3 ml blood samples (A and B) were withdrawn in a row from the venous lumen; a third blood sample (C) was withdrawn from a peripheral vein, and the 20 ml of blood in the syringe was returned to the patient. Patient to control ratios of activated partial thromboplastin time (aPTT) in samples A, B, and C were 2.87 +/- 1.04, 2.02 +/- 0.85, and 1.06 +/- 0.14, respectively (p < 0.002 comparing A to B and B to C). In these patients, we also studied the effect of the same HS on the aPTT, 10 minutes after the filling of the DLHCs postdialysis. A blood sample (H1) was withdrawn at the end of the session; 10 minutes after injecting each lumen of the DLHC with a 2 ml HS containing 3,750 IU of heparin, a second blood sample (H2) was drawn from a peripheral vein. The aPTT ratios in samples H1 and H2 were 1.15 +/- 0.13 and 3.58 +/- 0.61 respectively (p < 0.0001). We concluded that even after the aspiration of 15 ml from the venous lumen of a DLHC filled with a 2 ml HS containing 3,750 IU of heparin, the next blood sample remains contaminated by heparin. Filling each lumen of a DLHC with the same HS results in a significant increment of the aPTT 10 minutes later.

The effect of long-term intravenous high dose B-complex vitamins with or without folic acid on serum homocysteine in hemodialysis patients.

BACKGROUND: Many regimens using different doses of folic acid (FA) alone or with supplementation of B-complex vitamins (BCV) have been tested for the reduction of total homocysteine (tHcy) levels in hemodialysis (HD) patients. BCV are usually administered orally and for a short period. In the present study, we assessed the effect of long-term intravenous (IV) BCV on serum tHCy levels in HD patients, and the effect produced by moderate oral supplementation with FA. METHODS: In a cohort of 37 patients under chronic HD treatment for a mean of 50.2 +/- 46.7 months, serum concentrations of tHcy, folate and vitamin B12 were determined at the end of four sequential periods: (A) three months without any FA supplementation, (B) three months with oral supplementation of 5 mg of FA three times weekly, (C) six months without FA supplementation, and (D) three months without BVC or FA supplementation. From the start of HD treatment and throughout the study until the beginning of period D, patients received a standard IV dose of BCV (B1 250 mg + B6 250 mg + B12 1.5 mg) three times per week, post-dialysis. RESULTS: At the end of period B, mean serum tHcy levels were significantly lower than in periods A and C (13.7 +/- 3.6 micromol/L vs 19.6 +/- 10.8 micromol/L and 21.3 +/- 9.4 micromol/L, respectively, p < 0.001) and mean serum folate levels were significantly higher (20.7 +/- 7.4 ng/mL vs 5.0 +/- 2.8 ng/mL and 4.5 +/- 1.4 ng/mL, respectively, p < 0.01). At the end of period D, mean serum tHcy levels were significantly higher than in all the previons periods (29.3 +/- 13.5 micromol/L, p < 0.001). Twenty-six of the 37 patients (70.2%) had normal (< 15 micromol/L) serum tHcy levels at the end of period B and only one (2.7%) had normal tHcy at the end of period D. Mean serum vitamin B12 levels at the end of periods A, B and C were 100 times the usual normal values. At the end of period D, although significantly lowered (p < 0.001), they remained above the normal range. CONCLUSIONS: Long-term high-dose BCV IV three times a week post-dialysis reduced serum tHcy levels only when combined with oral FA supplementation.

Plasma exchange in patients with toxic epidermal necrolysis.

We describe our experience with plasma exchange (PE) therapy in 13 patients with drug-induced toxic epidermal necrolysis (TEN), 4 of whom had malignant disorders. Skin lesions covered 17% to 100% of total body surface area and 1 to 4 mucous membranes were involved. None of the patients was hospitalized in a burn unit. The patients underwent from 2 to 5 PE sessions (mean 3.4 +/- 0.2 standard error of mean [SEM], median 3) exchanging 6.6 to 17.6 L of plasma (mean 10.1 +/- 0.7 SEM, median 10). PE sessions were carried out every other day in 8 patients and daily in 5. Three patients died (23%) while the remaining 10 (77%) had a full recovery. Plasmapheresis may be an effective treatment in patients with drug-induced TEN hospitalized outside a burn unit.