Reduction Of Fibrinogen Research Articles

Heparin Induced Extracorporeal LDL Precipitation (H.E.L.P.) in Treatment of Tinnitus: A Randomised, Multicentre Trial

Background: At the beginning, cochlear tinnitus seems to arise from a dysfunction of cochlear outer hair cells. Similar to other inner ear disorders a disturbance of cochlear microcirculation is one of the most frequently discussed reasons. Animal studies and clinical evidence show a negative effect of high cholesterol and fibrinogen on hearing function. Acutely lowering serum LDL and fibrinogen by means of LDL and fibrinogen apheresis increases cochlear blood flow and has been proven to be effective in treatment of idiopathic sudden sensorineural hearing loss. Therefore we aimed to determine whether acute reduction of plasma fibrinogen and serum LDL is effective for treatment of subacute tinnitus. Methods: Between January, 2004 and December, 2006 we included patients of 18 through 80 years of age suffering from subacute cochlear tinnitus between 3 to 12 months on one or both ears and having serum LDL-cholesterol between 130 and 190 mg/dl. Tinnitus was evaluated using a standardised questionnaire designed by Goebel and Hiller. Patients meeting inclusion criteria were provided with the HMG-CoA reductase inhibitor simvastatin 40 mg once daily for 3 months. This procedure was done due to ethical reasons to reduce cholesterol and LDL non invasively in a first step. After 3 months tinnitus was re-evaluated and patients were excluded from the study if severity fell by more than 20 on the tinnitus score. 27 included participants were randomly assigned in a one to one ratio either to triple fibrinogen/LDL apheresis or triple sham therapy. Differences between tinnitus score on the day of randomisation and after 12 weeks were used as main outcome measure. Development of tinnitus score after every treatment, differences in loudness and frequency of tinnitus (masking and matching) after every treatment and after 12 weeks and the development of hearing thresholds after 12 weeks were used as secondary outcome measures. Findings: Main outcome measure tinnitus score 12 weeks after first therapy showed no significant differences between the groups. Though, there was a strong tendency towards an relieve of tinnitus in the apheresis group (p = 0.069 for the difference of the baseline value and the 12 weeks value between apheresis vs sham-therapy). Neither pure tone thresholds after 12 weeks, nor tinnitus masking and matching after every therapy and after 12 weeks showed significant differences between the groups. Conclusions: In our study, all patients suffered from subacute tinnitus and tinnitus score was stable or slightly worse in the placebo group over time. The improvement of tinnitus score in the apheresis group – although not statistically significant – is therefore a remarkable observation. For a more conclusive evaluation of this observation further studies with a larger number of patients should be conducted.

Fibrinogen Apheresis in the Treatment of Peripheral Arterial Disease

Background: Fibrinogen is mainly responsible for determining the viscosity of whole blood. In peripheral arterial disease (PAD) the fibrinogen concentration seems to affect the microcirculation flow. Aim: To study the effects of an abrupt reduction of fibrinogen on the hemodynamics of the lower extremities and the clinical picture of patients with PAD. Methods: Ten patients affected by various stages of PAD underwent 1 session of fibrinogen apheresis (TheraSorb, Miltenyi Biotec, Germany). Laboratory parameters of endothelial activation were assessed before and after the session, as well as walking distance (WD), the ankle-brachial index and laser Doppler flowmetry. Results: A significant reduction in the laboratory parameters was observed: fibrinogen (50%), total cholesterol (18%), LDL cholesterol (24%), sE-selectin (23%), sICAM-1 (19%) and sVCAM-1 (10%). The procoagulant factors, factor VIII and von Willebrand factor, did not vary significantly. Both pain-free and total WD were significantly improved (p < 0.003 and p <0.006, respectively), the ankle-brachial index remained unchanged, and laser Doppler flowmetry showed a modest but not significant increase. Conclusions: Fibrinogen apheresis allowed us to study the effects of an acute modification of fibrinogen in PAD, on both some aspects of the endothelial function and on the hemodynamics, demonstrating an improvement of WD and a minimal increase in the skin microcirculation.

Optimal timing for antihypertensive dosing: focus on valsartan.

Some specific features of the 24 h blood pressure (BP) pattern are linked to the progressive injury of target tissues and the triggering of cardiac and cerebrovascular events. In particular, many studies show the extent of the nocturnal BP decline relative to the diurnal BP mean (the diurnal/nocturnal ratio, an index of BP dipping) is deterministic of cardiovascular injury and risk. Normalization of the circadian BP pattern is considered to be an important clinical goal of pharmacotherapy because it may slow the advance of renal injury and avert end-stage renal failure. The chronotherapy of hypertension takes into account the epidemiology of the BP pattern, plus potential administration-time determinants of the pharmacokinetics and dynamics of antihypertensive medications, as a means of enhancing beneficial outcomes and/or attenuating or averting adverse effects. Thus, bedtime dosing with nifedipine gastrointestinal therapeutic system (GITS) is more effective than morning dosing, while also reducing significantly secondary effects. The dose-response curve, therapeutic coverage, and efficacy of doxazosin GITS are all markedly dependent on the circadian time of drug administration. Moreover, valsartan administration at bedtime as opposed to upon wakening results in improved diurnal/nocturnal ratio, a significant increase in the percentage of patients with controlled BP after treatment, and significant reductions in urinary albumin excretion and plasma fibrinogen. Chronotherapy provides a means of individualizing treatment of hypertension according to the circadian BP profile of each patient, and constitutes a new option to optimize BP control and reduce risk.

Major Obstetric Haemorrhage in Late Termination of Pregnancy in Eight Women.

Eight patients were referred from a private clinic between August 2003 and May 2004 for management of severe uncontrolled bleeding after late second trimester termination of pregnancy (TOP). TOP was perfomed at a mean gestation period of 21.4 weeks (median 21 weeks, 21–23 weeks) and was performed in 2 stages. Stage 1 comprised cervical dilatation, rupture of membrane, severing the cord and insertion of laminara. 24 hours later a dilatation and evacuation procedure was carried out. Mean age was 24.25 years (range 17–35). None of the women had any previous bleeding problems. Mean pre-operative Haemoglobin was 10.5 gm/dl (8.7 to 12.2 gm/dl). 1 patient had a preoperative clotting screen and this was normal. The pattern of bleeding was as follows: PV bleed 8/8, generalised bleed 2/8, haemodynamic failure 5/8. Median time to onset of bleeding after the second stage was 1.5 hours and median time to control bleeding was 9.5 hours. Details of coagulation screen and transfusion support are provided in tables 1 and 2. Factor VIIa was not approved for use in the hospital at that time.table 1coagulation parametersUPNnadir fibrinogen (1.8–4.5 g/l)hours to nadir from TOPhours to normal fibrinogenPT (9.6–11.6 secs)APTT (24–32 secs)platelets (150–400 × 109/l)10.4481816.737.220320.192722.654.810830.6771316.8384440.2151123.434.214550.355621.5784760.56123137.214170.573515.642.78880.94512.837.7144table 2blood product supportUPNcryoppt (units)FFP(units)RBC(units)platelets(units)11222220414131549440412520517261038718461822Obstetric interventions included hysterectomy (1), balloon occlusion (2) ERPC (1), hysterotomy (1), cervical tear repair (2) and vaginal pack (2). Obstetric cause of haemorrhage was identified to be uterine atony (4), retained products (2), uterine injury (2) and no identifiable cause (2). All women recovered fully.Results: The profound coagulopathy in these women was characterised by a reduction in fibrinogen that was out of proportion to the anomalies in other clotting parameters and platelet counts. Treatment with cryoprecipitate reversed this reduction and controlled the haemorrhage although 5/8 patients required significant surgical intervention.Conclusions:The coagulation anomalies in these women are indicative of a defibrination syndrome that differs from DIC in the disproportionate reduction in fibrinogen level and the relatively rapid and complete resolution with blood product replacement and treating uterine pathology.Two stage TOPs in late second trimester is associated with significant morbidity.

Inhibition of integrin αvβ3 reduces blood–brain barrier breakdown in focal ischemia in rats

Ischemic stroke is a major cause of morbidity and mortality in industrialized nations. We tested the effect of postischemic treatment of cyclo-RGDfV (cRGDfV), a selective inhibitor of integrin alphavbeta3, in the middle cerebral artery occlusion (MCAO) model of ischemic stroke in rats. Rats were randomly divided into three groups: sham operation (n = 13), MCAO with no treatment (n = 18), and MCAO with cRGDfV treatment (n = 28). Focal ischemia was induced with the suture occlusion method for 2 hr, and treatment was given 1 hr after reperfusion (3 hr after ischemia). All animals were sacrificed 24 hr after reperfusion. Assessment included neurological scores, infarction volumes, brain water content, Evans blue exudation, IgG exudation, histology, immunohistochemistry, and Western blotting. Treatment with cRGDfV ameliorated neurological deficits, reduced brain edema, and reduced exudation of Evans blue dye and IgG, but failed to reduce infarction volumes. Western blotting showed a reduction in phosphorylation of one subset of vascular endothelial growth factor (VEGF) receptors in the cRGDfV treatment group. Western blotting also demonstrated a significant reduction of fibrinogen in the cRGDfV treatment group. We conclude that poststroke treatment with cRGDfV reduces blood-brain barrier breakdown in focal ischemia, possibly through inhibition of VEGF-mediated vascular breakdown.

Salicylic acid activates sigma factor B by rsbU-dependent and -independent mechanisms.

Salicylic acid (SAL) may impact Staphylococcus aureus virulence by activating the sigB operon (rsbU-V-W-sigB), thus leading to reductions in alpha-toxin production and decreased fibronectin binding (L. I. Kupferwasser et al., J. Clin. Investig. 112:222-233, 2003). As these prior studies were performed in strain RN6390 (an rsbU mutant) and its rsbU-repaired variant, SH1000, the current investigation was designed to determine if the SAL effect occurs via rsbU- and/or rsbV-dependent pathways in an rsbU-intact S. aureus strain (FDA486). We thus quantified the transcription from two sigB-dependent promoters (asp23 and sarA P3) in FDA486 in response to SAL exposure in vitro, using isogenic single-knockout constructs of rsbU, rsbV, or rsbW and a green fluorescent protein reporter system. SAL induced sarA P3 and asp23 promoter activities in a dose-dependent manner in the parental strain. In contrast, sigB activation by SAL was progressively more mitigated in the rsbU and rsbV mutants. As predicted, SAL caused significant reductions in both alpha-toxin production and fibrinogen and fibronectin binding in the parental strain. The extent of these reductions, compared with the parent, was reduced in the rsb mutants (rsbV > rsbU), especially at low SAL concentrations. Since generation of the free SigB protein usually requires a sequential rsbU-V-W-sigB activation cascade, the present phenotypic and genotypic data suggest key roles for both rsbU and rsbV in SAL-mediated activation of sigB in strains with a fully intact sigB operon.

Malformations veineuses et coagulopathie

Activation of the coagulation process is frequently encountered in patients with venous vascular malformations and results in the local formation of clots and the consumption of components of the coagulation process (platelets, clotting factors). This activation accounts for multiple biological abnormalities such as the elevation of the D-dimers, reduction of fibrinogen and platelets count and less frequently a local intravascular coagulation (LIC). This process seems to be responsible for the local painful symptoms. In case of LIC, bleeding complications may be observed. Therapeutically, antithrombotic treatment with low-molecular weight heparin can improve the local coagulopathy with beneficial effects on blood tests disturbances, pain and bleeding tendency.

Cardiovascular disease and Alzheimer's disease: common links

Growing evidence supports a strong and likely causal association between cardiovascular disease (CVD), and its risk factors, with incidence of cognitive decline and Alzheimer's disease. Individuals with subclinical CVD are at higher risk for dementia and Alzheimer's. Several cardiovascular risk factors are also risk factors for dementia, including hypertension, high LDL cholesterol, low HDL cholesterol and especially diabetes. Moderate alcohol appears to be protective for both CVD and dementia. In contrast, inflammatory markers predict cardiovascular risk, but not dementia, despite biological plausibility for such a link. The substantial overlap in risk factors points to new avenues for research and prevention.

Inhibition of Integrin αvβ3 Ameliorates Focal Cerebral Ischemic Damage in the Rat Middle Cerebral Artery Occlusion Model

Recent studies have shown that selective inhibition of specific subsets of intercellular adhesion molecules protects the brain during ischemia. We studied selective inhibition of integrin alphavbeta3 with cyclo [Arg-Gly-Asp-D-Phe-Val] (cRGDfV) in the rat middle cerebral artery occlusion model (MCAO). Rats were treated before and after MCAO with cRGDfV. Physiological parameters, expression of integrin alphavbeta3, infarction volume, brain water content, Evans Blue exudation, IgG exudation, histology, immunohistochemistry, and western blotting were studied in 4 groups of animals: sham operation (n=13), untreated (n=18), nonfunctioning peptide treatment (n=19), and cRGDfV treatment (n=27). Treatment with cRGDfV reduced infarction, reduced brain edema, reduced exudation of Evans blue and IgG, and prevented fibrinogen deposition. Western blotting showed reduction of phosphorylated Flk-1 (a vascular endothelial growth factor [VEGF] receptor), reduction of phosphorylated FAK (an intracellular kinase phosphorylated in the presence of VEGF), reduction of VEGF, and reduction of fibrinogen in the cRGDfV treatment group. The selective integrin alphavbeta3 inhibitor cRGDfV improves outcomes in the MCAO model by preserving the blood-brain barrier, which mechanistically may occur in a VEGF- and VEGF-receptor-dependent manner.

Treating to target patients with primary hyperlipidaemia:comparison of the effects of ATOrvastatin and ROSuvastatin (the ATOROS study)

ABSTRACTObjectives: In a 24-week, open-label, randomized, parallel-group study, we compared the efficacy and metabolic effects, beyond low density lipoprotein cholesterol (LDL-C)-lowering, of atorvastatin (ATV) and rosuvastatin (RSV) in cardiovascular diseasefree subjects with primary hyperlipidaemia, treated to an LDL-C target (130 mg/dL).Methods: After a 6‐week dietary lead-in period, patients were randomized to RSV 10 mg/day ( n = 60) or ATV 20 mg/day ( n = 60). After 6 weeks on treatment the dose of the statin was increased (to RSV 20 mg/day or ATV 40 mg/day) if the treatment goal was not achieved. A control group of healthy volunteers ( n = 60) was also included for the validation of baseline serum and urinary laboratory parameters. The primary outcome was the percentage of patients reaching the LDL‐C goal; secondary outcomes were changes in lipid and non-lipid metabolic parameters.Results: A total of 45 patients (75.0%) in the RSV-treated group and 43 (71.7%) in the ATV-treated group achieved the treatment target at the initial dose. Both regimens were generally well tolerated and there were no withdrawals due to treatment-related serious adverse events. Similar significant reductions in total cholesterol, LDL‐C, apolipoprotein (apo) B, triglycerides, apoB/apoA1 ratio, fibrinogen and high-sensitivity C‐reactive protein levels were seen. RSV had a significant high density lipoprotein cholesterol (HDL‐C)-raising effect and showed a trend towards increasing apoA1 levels. Glycaemic control and renal function parameters were not influenced by statin therapy. ATV, but not RSV, showed a significant hypouricaemic effect.Conclusions: RSV and ATV were equally efficacious in achieving LDL‐C treatment goals in patients with primary hyperlipidaemia at the initial dose and following dose titration. RSV seems to have a significantly higher HDL‐C-raising effect, while ATV lowers serum uric acid levels.

Blood viscosity, Raynaud's phenomenon and the effect of fibrinolytic enhancement.

The whole blood and corrected blood viscosity of 17 patients with Raynaud's phenomenon (8 with idiopathic Raynaud's phenomenon and 9 with scleroderma-associated Raynaud's phenomenon) have been compared with 12 normal controls. Viscosity has been measured with a Contraves LSV1 rotating viscometer and the Wells-Brookfield microviscometer at 37 degrees C and 25 degrees C and shear rates ranging from 0.775 s-1 to 230 s-1. Blood viscosity was higher at both the lower temperature and the lower shear rates but this change was the same in the patients as in the normal subjects. There was a significantly higher level of plasma fibrinogen in the patients with scleroderma with a significant increase in the corrected blood viscosity, but not the whole blood viscosity, at both temperatures and all shear rates. The percentage increase of viscosity at low temperatures in the patients was the same as the controls. No evidence was found to substantiate the hypothesis that Raynaud's phenomenon is caused by an excessive increase of blood viscosity at low temperatures. Treatment of 10 patients with stanozolol, a stimulator of fibrinolysis, reduced the plasma fibrinogen and increased the haematocrit did not change the whole blood viscosity. Hand blood flow increased. The improvement of hand blood flow was not therefore caused by change in blood viscosity secondary to the reduction of plasma fibrinogen.

Acute Effect of Rheopheresis on Peripheral Endothelial Dysfunction in Patients Suffering From Sudden Hearing Loss

Single low density lipoprotein (LDL) fibrinogen apheresis has shown beneficial effects in the treatment of patients with sudden sensorineural hearing loss (SSHL). Pathophysiologically, a microcirculatory disorder of the inner ear, probably caused by disturbed endothelial function, is discussed as a final common pathway of a variety of SSHL etiologies. Thus, we carried out a prospective pilot study on the efficacy of Rheopheresis on vascular function in these patients, embedded into an ongoing randomized controlled multicenter trial investigating the efficacy of Rheopheresis for the treatment of SSHL. Potential modulation of systemic endothelial dysfunction by Rheopheresis was examined by measuring flow-associated vasodilatation of the brachial artery (according to the criteria of the American College of Cardiology) in a small group of patients suffering from SSHL (N=6, 5m/1f, mean age 56+/-11 years) within the last 3 days. At baseline, five of the six patients with acute hearing loss showed endothelial dysfunction as evidenced by diminished flow-mediated vasodilatation (FMD<5%). After a single Rheopheresis treatment, flow-mediated vasodilatation improved significantly (from 3.9+/-3.6% to 7.2+/-2.4%, P=0.05, mean+/-SD, two-sided paired T-test). This was paralleled by a reduction in fibrinogen (364+/-216 mg/dL to 142+/-96 mg/dL, P=0.03), total cholesterol (228+/-23 to 98+/-10, P<0.0001) and LDL cholesterol levels (153+/-8 mg/dL to 83+/-23 mg/dL, P<0.01). Based on this case series we conclude that single Rheopheresis treatment might have an acute beneficial effect on endothelial dysfunction in patients suffering from SSHL.

LDL‐Apheresis Accelerates the Recovery of Nonarteritic Acute Anterior Ischemic Optic Neuropathy

Nonarteritic acute anterior ischemic optic neuropathy (NAION) is a disabling disease which impairs visual function. It is presumed to result from disturbances of microcirculation in the anterior portion of the optic nerve head due to hemodynamic factors derived from excessive blood viscosity, or restriction of the vasal lumen in hypertensive, hypercholesterolemic, diabetic patients. We aimed to determine whether acute reduction of plasma fibrinogen and serum low-density lipoprotein (LDL) cholesterol is effective for treatment of NAION. We recruited 11 patients (7 females, 4 males) with a mean age of 57.2 +/- 19.6 years. All except one of them presented risk factors for atherosclerosis. The mean values of LDL-cholesterol and fibrinogen before treatment were 144 +/- 32 mg/dL and 341 +/- 80 mg/dL, respectively. All were treated with standard therapy (prednisone, salicylate, pentoxiphyllin) and underwent three sessions of LDL-apheresis (HELP system-B Braun) that can reduce plasma LDL-cholesterol and fibrinogen by more than 50% in a very short time. In all patients we observed a drastic reduction of LDL cholesterol and fibrinogen and a clear improvement in the visual functional data. In fact, mean values of corrected vision increased from 3.7/10 +/- 3/10 to 7.9/10 +/- 2.2/10 (P = 0.002) after the third session, while the scotomatous portion of the visual field regressed after the first session, and in 5 patients further regressed after the third session. This improvement had remained stable after 3 months. Thanks to it's effect of antagonizing hemorheologic disorders of the ocular microcirculation, fibrinogen/LDL-apheresis seems to be an efficacious treatment of NAION.

Lipids and clotting factors during low dose transdermal estradiol/norethisterone use

Objective: To demonstrate the effects of 2-year transdermal continuous combined low-dose estradiol (0.025 mg/day) and norethisterone acetate (0.125 mg/day) on lipid/lipoprotein profile and coagulation/fibrinolysis. Methods: A double-blind, randomized, multicenter, parallel, 1-year trial enrolled 266 healthy women at least 2 years post menopause. Patients received either 0.025 mg estradiol and 0.125 mg norethisterone acetate daily or placebo transdermally. One hundred and thirty five women completed a second year open follow-up (96 had used Estragest TTS, 39 placebo during the first year), where all women had the estradiol/norethisterone patch. Lipid/lipoprotein profile and coagulation/fibrinolysis parameters were studied at 0, 24, 48, 72 and 96 weeks. Results: In women on estradiol/norethisterone total cholesterol, Lp(a) and VLDL cholesterol decreased significantly more than in the placebo group after 24 weeks and LDL cholesterol after 48 weeks. Women on estradiol/norethisterone had no change in HDL, triglycerides or Lp(a), an increased HDL/total cholestrol ratio and decreased LDL, VLDL and total cholesterol at 48 weeks compared to placebo. Women with active treatment also showed a significant reduction compared with the placebo group of Factor VII and antithrombin III at 24 and 48 weeks and a reduction of fibrinogen at 24 weeks. These changes persisted over the second year. Conclusions: A continuous combined low-dose transdermal patch daily delivering 0.025 mg estradiol and 0.125 mg norethisterone acetate provided beneficial effects on lipid/lipoprotein profile and coagulation/fibrinolysis. The changes were similar to those previously described after higher dose oral and transdermal estrogen/progestogen regimens.

Effects of prolonged strenuous exercise (marathon running) on biochemical and haematological markers used in the investigation of patients in the emergency department

Objectives: To investigate the effects of strenuous exercise on commonly used biochemical and haematological variables in subjects running the 2002 London marathon. Methods: 34 healthy volunteers (7 female, 27 male)...

Haemostatic and inflammatory biomarkers in advanced chronic heart failure: role of oral anticoagulants and successful heart transplantation.

Advanced chronic heart failure (CHF) is associated with abnormal haemostasis and inflammation, but it is not known how these abnormalities are related, whether they are modified by oral anticoagulants (OAT), or if they persist after successful heart transplantation. We studied 25 patients with CHF (New York Heart Association class IV, 10 of whom underwent heart transplantation) and 25 age- and sex-matched healthy controls by measuring their plasma levels of prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin (TAT) complexes, tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), D-dimer, factor VII (FVII), fibrinogen, von Willebrand factor (VWF), tumour necrosis factor (TNF), soluble TNF receptor II (sTNFRII), interleukin 6 (IL-6), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), endothelial-selectin (E-selectin) and thrombomodulin. CHF patients had higher plasma levels of TAT, D-dimer, t-PA, fibrinogen, VWF, TNF, IL-6, sTNFRII, sVCAM-1 (P = 0.0001), sICAM-1 (P = 0.003) and thrombomodulin (P = 0.007) than controls. There were significant correlations (r = 0.414-0.595) between coagulation, fibrinolysis, endothelial dysfunction and inflammation parameters, which were lower in those patients treated with OATs. Heart transplantation led to reductions in fibrinogen (P = 0.001), VWF (P = 0.05), D-dimer (P = 0.05) and IL-6 levels (P = 0.05), but all the parameters remained significantly higher (P = 0.01-0.0001) than in the controls. Advanced CHF is associated with coagulation activation, endothelial dysfunction and increased proinflammatory cytokine levels. Most of these abnormalities parallel each other, tend to normalize in patients treated with OATs and, although reduced, persist in patients undergoing successful heart transplantation, despite the absence of clinical signs of CHF.

Lipidfiltration––safe and effective methodology to perform lipid-apheresis

Familial hypercholesterolemia (FH) not adequately responding to diet and drug therapy represents an indication for extracorporeal lipid-apheresis, which has become an highly effective and approved therapy for those patients in several countries. Based on different methodology, five treatment options of lipid-apheresis exist and are in widespread practical use covered by regular reimbursement in Germany. All methods are safe and demonstrate equivalent efficacy of reducing LDL cholesterol with respect to the single apheresis session as well as during long-term treatment. Therefore German reimbursement guidelines leave the choice of the method to the discretion of the apheresis center. Related to properties of the used technology all methods exhibit characteristic patterns of additional plasma protein elimination, which do not impair, but in part may increase the therapeutic benefit of lipid-apheresis. Fibrinogen reduction has to be mentioned as an example. The Lipidfiltration system is based on plasmafiltration previously referred to as membrane differential filtration (MDF), synonymous with double filtration plasmapheresis (DFPP). The new term Lipidfiltration was the result of technological progress in the manufacturing process of the plasmafilter resulting in enhanced sieving characteristics and capacity. The Lipidfiltration system is completed by a specifically designed therapy machine with optimised performance characteristics.

813-3 Reduction of plasma cholesterol and fibrinogen by H.E.L.P. apheresis increases myocardial perfusion in heart transplant patients

813-3 Reduction of plasma cholesterol and fibrinogen by H.E.L.P. apheresis increases myocardial perfusion in heart transplant patients

The Efficacy and Safety of the New Heparin‐induced Extracorporeal Low‐density Lipoprotein Precipitation System (Plasmat Futura) in Comparison with the Currently used System (Plasmat Secura)

The aim of the present study was to examine whether the recently introduced heparin-mediated extra-corporeal low-density lipoprotein precipitation (HELP) apheresis system Plasmat Futura (since 2001) was comparable to Plasmat Secura system, used to date, in its efficiency to remove atherogenic components, its ease of handling and operating as well as clinical safety and patient compliance. Coronary heart disease (CHD) patients (N = 21) were first treated with Plasmat Secura system and 13 of them were then randomly switched over to the upgraded Plasmat Futura system. Eight patients remained on Secura system. All together, 40 Futura treatments and 40 Secura treatments were performed. Blood samples were collected immediately before and after each apheresis therapy. Our data showed no significant differences in the reduction of plasma low-density lipoprotein, lipoprotein (a) and fibrinogen by Plasmat Futura and Secura system (P > 0.05). However, the major advantages of Plasmat Futura system are the ready-to-use sterile dialysis solutions instead of reverse osmosis device in Plasmat Secura, which ensures flexibility and lower risk of cross infections. Long-term tolerance and safety parameters showed no significant difference (P > 0.05). On the basis of our studies. Plasmat Futura system is easy to use, shows no adverse events and is comparable to Plasmat Secura in its capacity to remove proatherogenic plasma factors.

Improved treatment of sudden hearing loss by specific fibrinogen aphaeresis.

The etiology of sudden sensorineural hearing loss is still unclear and is thought to result from disturbances of microcirculation, infectious causes, or autoimmune disorders. So far standard therapy did not show clear improvement over spontaneous remission rate, which is assumed to be about 50% [Nakashima et al., Acta. Otolaryngol. Stockh. 514:14-16, 1994; Schuknecht and Donovan, Arch. Otorhinolaryngol. 243:1-15, 1986; Harris and Sharp, Laryngoscope 100:516-524, 1990; Mayot et al., Clin. Immunol. Immunopath. 68:41-45, 1993; Gussen, Ann. Otol. Rhinol. Laryngol. 85:94-100, 1976]. Elevated blood viscosity due to high fibrinogen levels is supposed to cause decreased cochlear blood flow and thus initiate sudden hearing loss. The specific lowering of fibrinogen immediately decreases plasma viscosity exactly to the desired extent and should lead to improved cochlear blood flow [Suckfüll et al., Acta. Otolaryngol 119:763-766, 1999; Suckfüll, Lancet 360:1811-1817, 2002; Walch et al., Laryngol. Rhino. Otol. 75:641-645, 1996; Suckfüll et al., Otol. Neurotol. 23:309-311, 2002]. In a prospective uncontrolled pilot study on 36 patients with unilateral sudden onset sensorineural hearing loss (SHL) we tried to establish that 1-3 specific fibrinogen aphaereses alone improve recovery of hearing and that it is possible to lower fibrinogen to the target of 80-100 mg/dl without important side effects. Pure tone audiometry was carried out immediately before and after each aphaeresis as well as at 2 and 4 weeks and 6 months after treatment. Sixteen patients recovered spontaneously before undergoing fibrinogen adsorption. All 20 aphaeresis patients improved during immunoadsorption; in 60% of patients auditory thresholds returned to normal after the first immunoadsorption and treatment could be discontinued, in another 20% of patients complete recovery was reached after 4 weeks. The mean plasma fibrinogen concentration of the 20 patients before the first aphaeresis session was 308.1 +/- 51.5 mg/dl. Immediately after the first treatment session, the fibrinogen concentration was lowered to 100.7 +/- 25.3 mg/dl (P < 0.001). The second and third sessions also showed highly significant reductions in plasma fibrinogen. No important side effects were seen. In conclusion, specific fibrinogen adsorption is a promising new treatment modality that should be tested in a prospective, randomized controlled trial in patients with sudden hearing loss.