Manfred Walzl

Improved neurological recovery of cerebral infarctions after plasmapheretic reduction of lipids and fibrinogen.

Background and Purpose High fibrinogen levels have been assessed in cerebrovascular disease with a direct relation to both plasma and whole-blood viscosity, as well as cerebral blood flow. Heparin-induced extracorporeal low density lipoprotein precipitation (HELP) is a new method that safely and effectively reduces fibrinogen and plasma lipoproteins and improves blood flow properties. Methods We studied 26 patients with acute embolic stroke and 22 with multi-infarct dementia. Each received two treatments with HELP within 8 days. Each patient had measurement of the important blood constituents and evaluation of changes in clinical signs and symptoms related to their cerebrovascular disease. Results Each HELP treatment safely produced an immediate and significant reduction in rheological measures, including fibrinogen (P < .001), whole-blood viscosity at high and low shear rates, plasma viscosity, and red cell transit time (P < .01 each). Total cholesterol, low density lipoprotein (P < .0001 each), lipoprotein (a) (P < .003), and triglycerides (P < .0001) were also reduced. The treated group in both the acute stroke group and the multi-infarct group showed improvement relative to the untreated control subjects in Mathew scale, Mini-Mental State Examination, and activities of daily living test scores. These uniform improvements persisted at least 3 days past the second HELP treatment. Conclusions These results support the hypothesis that the improved hemorheologic property of blood is an important factor in clinical recovery as well as basic neurological function.

Effects of ameliorated haemorheology on clinical symptoms in cerebrovascular disease

Cerebrovascular disease (CVD) is associated with high fibrinogen levels and lipid fractions leading to an increase of both plasma and whole blood viscosity as well as raised aggregability of blood cells. One important goal in the treatment of cerebral multiinfarct dementia (MID) therefore should be to reduce fibrinogen and lipoproteins and thereby to improve the haemorheological state. The effect of heparin-induced extracorporeal LDL precipitation (H.E.L.P.), a method for safe and immediate reduction of parameters relevant to haemorheology, such as plasma fibrinogen and the lipoproteins, was investigated in 98 patients with MID. All the patients underwent two H.E.L.P. applications within 8 days. The impact of H.E.L.P. on CVD was studied by changes of laboratory data and by evaluation of clinical symptoms before and after treatment. Each H.E.L.P. session caused an immediate, safe and significant reduction of important rheological parameters such as fibrinogen (P < 0.001), whole blood viscosity at high and low shear rate, plasma viscosity and red cell transit time (P < 0.01 each). Also total cholesterol and low density lipoprotein (P < 0.0001 each), lipoprotein (a) (P < 0.003) and the triglycerides (P < 0.0001) had been reduced. The results in laboratory measurement were followed by a statistically significant improved neurologic recovery, represented in the values of the Mathew Scale, the Mini Mental State Examination and the Activities-of-Daily-Living-Test. These results can indicate the importance and influence of haemorheology on clinical symptoms in CVD.

Application of HELP in nonarteritic anterior ischemic optic neuropathy: A prospective, randomized, controlled study

Abstract• Background: Heparin-induced extracorporeal LDL/fibrinogen precipitation (HELP) eliminates selectively fibrinogen, LDL, cholesterol, triglycerides and LP(a) from blood plasma using extracorporeal circulation. The reduction of fibrinogen and LDL by about 50% after only one procedure immediately improves the hemorheological situation. • Method: In a prospective, randomized, controlled study over a period of 3 months, 40 patients with nonarteritic ischemic optic neuropathy (NAION) were randomly assigned to either HELP or hemodilution therapy to determine the efficacy of these two treatments on visual acuity and fields. • Results: After transformation of the Snellen acuity into logMAR units the statistical analysis did not show a significant difference between the two groups (P=0.48). An increase of the visual acuity by two or more lines was obtained in 9 patients (47.4%) of the HELP group, 10 (52.6%) remained stable and none got worse. In the hemodilution group, visual acuity increased in patients (33.4%), 9 (42.8%) remained stable and 5 (23.8%) experienced a decrease. The calculated mean sensitivity of visual fields at baseline improved statistically significantly (P<0.01) in the HELP group from 6.83 ±4.52 dB to 8.27±4.89 dB, but did not change significantly in the hemodilution group (6.25 ± 4.12 dB to 6.12±3.92 dB). • Conclusion: The HELP system seems to be safe and more effective than hemodilution in improving the hemorheological and the functional situation in NAION and could be a promising regimen in the treatment, of NAION.

First experiences with the heparin-induced extracorporeal low-density lipoprotein precipitation in the treatment of critical limb ischaemia: a new therapeutical approach?

The heparin-induced extracorporeal low-density lipoprotein (LDL) precipitation (HELP) system is based on the fact that besides lipoproteins even fibrinogen, which seems to be a very important factor in pathogenesis of peripheral arterial disease, is precipitated by high-dose heparin at acid pH values. The elimination of excess fibrinogen and lipoproteins, in particular LDL, leads to a markedly improved microcirculation. The restoration of the latter obviously enabled us to perform limb-saving surgical procedures instead of mutilating amputations. 12 patients suffering from peripheral arterial disease were submitted to 18 HELP treatments in each case instead of having their critically ischaemic legs removed. Surgery could be limited to necrosectomy only and the wounds were either primarily sutured or covered with skin grafts. We were able to avoid 13 amputations in these 12 patients who could finally walk out of the hospital. HELP treatment was free of side effects in all of them.

Increased Cerebral Perfusion following Reduction of Fibrinogen and Lipid Fractions

High levels of plasma fibrinogen in cerebrovascular disease cause deterioration in the hemorheologic pattern, microcirculation and cerebral perfusion. We compared the value of heparin-induced extracorporeal LDL precipitation (HELP) which is a method that safely and effectively reduces plasma fibrinogen and lipoproteins and so improves the hemorheologic pattern and blood flow properties. Regional cerebral blood flow (rCBF) was measured by the 133Xe SPECT clearance method. After first measuring rCBF, 15 patients suffering from cerebral multi-infarct disease underwent a single HELP application. One hour later a second measurement of rCBF was performed. Fifteen other patients with similar clinical symptoms and findings on CAT scans who were not subjected to HELP served as controls. The HELP treatment produced an immediate and statistically significant reduction of all parameters relevant to hemorheology, such as plasma fibrinogen, whole blood viscosity at both high and low shear rate, plasma viscosity, and red cell transit time. Total cholesterol, low density lipoprotein, and triglycerides were also reduced. The treated group showed 9.7-19.9% increased rCBF in different vascular regions examined relative to the untreated controls. The results obtained indicate that HELP has a potent effect in a situation demanding rapid and significant improvement of the blood flow.

Influence of a Single HELP Application on Hemorheology and Retinal Hemodynamics

The heparin-induced extracorporeal low-density lipoprotein precipitation (HELP) eliminates selectively fibrinogen, total cholesterol, low-density lipoproteins (LDL) and triglycerides and improves hemorheology. We investigated the hemodynamic changes in 10 patients without ocular diseases performing a video fluorescein angiography after a single HELP procedure measuring the arm-retina time (ART) and the arteriovenous passage time (AVP). Laboratory parameters such as fibrinogen, cholesterol, LDL, triglycerides, red cell transit time, plasma and whole-blood viscosity were determined and retinal circulation was measured immediately before and after the HELP application. All of the laboratory parameters were lowered significantly. The ART was unaffected by the HELP procedure; however, there was a significant AVP reduction from 2.41 +/- 0.49 to 1.97 +/- 0.47 (p < 0.005). These results support the hemorheological and hemodynamic efficiency of the HELP system in microcirculatory diseases.

Extracorporeal fibrinogen and platelet precipitation as a new haemorheological treatment for acute stroke

In thromboembolic brain infarctions high fibrinogen levels are associated with an increase of both plasma and whole blood viscosity as well as increased aggregability of blood cells. This decreases cerebral perfusion and might reduce blood flow in the penumbra surrounding infarction. An important goal in the treatment of acute cerebral infarction is to reduce fibrinogen and thereby improve the haemorheological state. Heparin-induced extracorporeal low-density lipoprotein/fibrinogen precipitation (HELP) appears to be successful in achieving this. Such treatment reduces lipid fractions, including total cholesterol, low-density lipoproteins (LDL) and triglycerides (p < 0.0001 each), as well as fibrinogen (p < 0.0001) in a safe and efficacious manner. Whole blood and plasma viscosity are also improved when measured by oscillo-rheometry. Furthermore, the number and aggregation tendency of blood cells is influenced positively as determined by Coulter counting and aggregometry. HELP improves the haemorheological profile to a degree which has not been achieved by haemorheologically active substances.

Heparin-Induced Extracorporeal Fibrinogen/LDL Precipitation (HELP): A Promising Regimen for the Treatment of Vascular Diseases:

Current management of atherosclerotic diseases consists primarily of medical therapy designed to increase oxygen supply to the heart, the brain, retinal vessels, or lower limbs. The development of these diseases is based on atherosclerotic changes induced by risk factors such as elevated levels of fibrinogen and lipoproteins. These risk factors are related to a dramatic deterioration of the hemorrheologic pattern, which reduces perfusion. Consequently, attempts are now being made to treat ischemia via hemorrhe ological intervention. A new treatment modality utilizing the heparin-induced extracor poreal low-density lipoprotein (LDL) precipitation (HELP), offers the possibility of obtaining therapeutic success not only in cases of severe hypercholesterolemia but also in the field of hemorrheology. With HELP a safe and rapid reduction of fibrinogen and lipid fractions has become feasible, thus providing acute improvements of red cell aggregation, of the filterability of blood cells, of whole-blood and plasma viscosity, and thereby of microcirculation. Because cerebrovascular diseases are known to be related to distur bances of the hemorrheological situation, the HELP system is used in the Department of Electrobiology of Graz for the treatment of acute stroke, cerebral multiinfarct disease, and occlusions of retinal arteries.

Results of a two-month follow-up after single heparin-induced extracorporeal LDL precipitation in vascular dementia.

A trial was undertaken with 44 patients with the diagnosis of cerebral multi-infarct dementia. Of these, 24 had been exposed to single heparin-induced extracorporeal low-density lipoprotein (LDL) precipitation (HELP) whereby an immediate, safe, and statistically significant reduction of total cholesterol, LDL, triglycerides, fibrinogen (<0.0001 each), lipoprotein (a) (p < 0.003), whole-blood viscosity (p < 0.005 at high shear and p < 0.007 at low shear rate), plasma viscosity (p < 0.0002) and red cell transit time (p < 0.0001) to between 17.9% and 58.8% could be obtained within 2 h. Even an amelioration in the neuropsychological state, objectified by the Mathew Scale (p < 0.01), the Mini-Mental State Examination (p < 0.03), and the Activities-of-Daily-Living Test (p < 0.05) was observed. Despite the fact that the laboratory parameters had reached their pretreatment values within 10 days after the HELP procedure, the scores of the test battery remained stable during a follow-up period of 2 months. Within a control group (n = 20), no changes in laboratory data or in test scoring could be observed.

HELP Application in Multi-Infarct Dementia

HELP is capable of lowering LDL, cholesterol, triglycerides, and fibrinogen. It has been proven that HELP application has an impact on MID by decreasing plasma fibrinogen, cholesterol, LDL, triglycerides, thus also reducing whole-blood plasma viscosity, plasma fibrinogen, and red cell transit time. It has been shown that a single HELP treatment in MID is followed by an improvement of the scores obtained from the rating scales employed (Mathew, Mini Mental State Examination, Activities of Daily Living) for as long as 10 days, which was supported by comparison with the scores of a control group. Repeated HELP application (up to five) within 40 days led to an improvement of the test battery values in comparison with base values and those of the respective control group. Further applications (up to 10) of plasmapheresis, however, remained without any remarkable effect on the rating scales employed, with the difference from the corresponding control groups remaining the same.