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Biomedical subjects

A Haass

Publications and source records attributed to A Haass.

At least 37 records · Page 2Linked to original sources
PubMed1997

Increased haemorrhagic risk after repeated infusion of highly substituted medium molecular weight hydroxyethyl starch.

Infusion of the large volumes of high molecular weight hydroxyethyl starch (HES) has been know to lead to coagulation disorders. Medium molecular starch is considered a safe alternative, even after repeated administration. In 10 patients with cerebrovascular diseases, a 10-day hemodilution was carried out using 10% HES 200/0.62. Initially, a loading dose of 500 ml was administered once over 45-60 min, followed by 500 ml maintenance dose per day for 10 days. Its high intravascular molecular weight (120,000 D) showed that cleavage of the starch is slowed due to the higher degree of substitution. The continuous increase of HES-serum concentration to 27.7 mg/ml gave evidence of a cumulation of poorly degradable molecules. Although this caused a prolonged volume effect, plasma viscosity and erythrocyte aggregation were influenced in an unfavourable way. The negative effects were not evident in their influence on the coagulation system. Under therapy, a significant 42.8% increase (p < 0.01) in activated partial thromboplastin time occurred. Factor VIII:C, von Willebrand ristocetin co-factor and von Willebrand factor antigen dropped during the therapy below the hemostasiological limit of 30% (p < 0.01), and in some patients below 10%. A high degree of substitution, particularly after repeated infusion, leads to a cumulation of large molecules that are difficult to break down and which unfavourably affect rheological and hemostasiological parameters.

Blood Coagulation↗
PubMed1997

Coagulation disorders caused by hydroxyethyl starch.

Initially, hydroxyethyl starch (HES) was only characterized by its in vitro molecular weight (MW). This is not sufficient because HES is degraded in vivo. One relevant parameter that predicts the rate of enzymatic breakdown is the degree of substitution, a measure of the average number of hydroxyethyl groups per glucose unit. The higher this degree of substitution, the slower the break-down. In addition, because the glucose units can be substituted at carbon 2, 3 and 6, different substitution patterns are possible. They are classified by their C2/C6 hydroxyethylation ratio. A higher C2/C6 ratio results in less metabolism of the starch in vivo and results in a larger in vivo MW. This in turn affects therapy, because the larger the in vivo MW, the longer is the duration of the volume effect of HES. Of particular importance is the fact that HES with a high in vivo MW affects factor VIII/von Willebrand factor which can lead to an acquired von Willebrand syndrome. During a 10-day volume therapy with a medium-MW HES 200, a form that is difficult to metabolize, we observed an 80% drop in factor VIII/von Willebrand factor. Therapy with a medium-MW HES 200, a form that is easily degraded, and therapy with a low-MW HES 70 did not result in a relevant decline of factor VIII/von Willebrand factor. This explains why hemorrhagic complications have been observed repeatedly in the United States after therapy with HES infusions, some of them lethal. In the United States high-MW HES 480 which is difficult to degrade is most frequently used and results in a larger in vivo MW and subsequent decrease in factor VIII/von Willebrand factor levels. In Europe, medium-MW HES 200 that is easily degraded and low-MW HES 70 are preferred. In the future, HES should be characterized by the in vivo, not the in vitro MW.

Blood Coagulation Disorders↗
PubMed1996

Cardiac output in patients with acute stroke.

It is well known that blood pressure is elevated during acute stroke. Despite its importance for cerebral haemodynamics, cardiac output (CO) has been determined only in individual cases during acute stroke. We measured CO and blood pressure in patients with no history of heart disease who suffered from acute stroke (n = 30) and in a control group comparable with regard to age, gender and cardiac health (n = 30). CO, blood pressure and heart rate were significantly (P < 0.01) higher in the group of stroke patients than in the control group. There was a tendency for more time to have elapsed between the onset of symptoms and measurements, the higher the CO [b = 0.08 l/min per hour (-0.01; 0.17)]. Adjusted for age in a multiple regression model, the regression coefficient was significant (CO = 10.35 +0.094 x time -0.077 x age). The present study shows for the first time that patients with a healthy cardiovascular system who suffer from acute stroke have a higher CO than a group of comparable controls.

Acute Disease↗
PubMed1996

All medium starches are not the same: influence of the degree of hydroxyethyl substitution of hydroxyethyl starch on plasma volume, hemorrheologic conditions, and coagulation.

BACKGROUND: After the application of high volumes of high-molecular-weight starch (hetastarch), bleeding complications have repeatedly been observed. Later studies showed that the application of medium-molecular-weight starch led to far fewer disturbances of the blood coagulation system. However, the relationships among the degree of hydroxyethyl substitution, the rate of degradation, and the average in vivo molecular weight have not been investigated. STUDY DESIGN AND METHODS: A 10-day hemodilution treatment (n = 20) was carried out using two medium-molecular-weight hydroxyethyl starches (HES) with a degree of hydroxyethyl substitution of 0.5 and 0.62, respectively (10% HES 200 was used for a substitution of 0.5 and 6% HES 200 for a substitution of 0.62). After a loading dose of 500 mL was administered, 1000 mL of HES was infused daily for 4 days, and then 500 mL was infused daily for 6 days. RESULTS: The more highly substituted starch was broken down more slowly and eliminated renally. This resulted in a higher intravascular molecular weight than for the less highly substituted HES (120 vs. 84 kDa) and a greater increase in serum concentration (20.3 vs. 9.0 mg/mL). Initially, the more highly substituted 6-percent HES had a lesser effect on plasma volume (p < 0.01). Because of HES accumulation, there was no longer a significant difference between the starches by the end of treatment, even though a higher dose of the 10-percent low-substitution starch was infused. Six-percent HES caused an increase in plasma viscosity (+9%, p < 0.01) that was due to an accumulation of macromolecules. Ten-percent HES 200/0.5 had no effect on the coagulation system beyond the dilution effect. Six-percent HES, on the other hand, led to an acquired von Willebrand syndrome during the course of the 10-day therapy. Factor VIII function was reduced by 72.2 percent, von Willebrand ristocetin cofactor by 61.3 percent, and von Willebrand factor antigen by 64 percent (p < 0.01). CONCLUSION: It is the intravascular and not the initial (in vitro) molecular weight that determines the properties of HES. Especially after repeated administration, a high degree of hydroxyethyl substitution leads to an accumulation of macromolecules that affect hemorrheologic measures and the coagulation system just as adversely as high-molecular-weight starch does. Depending on the degree of substitution, medium-molecular-weight starches can have widely differing properties.

Blood Coagulation↗
PubMed1996

[Transcranial Doppler examination on effect of hemodynamics on cerebral autoregulation in acute cerebral infarct].

AIM: We treated 24 patients suffering from an acute ischemic stroke of the middle cerebral artery, with a hypervolemic hemodilution combined with dopamine/dobutamine. METHOD: The influence of blood pressure and cardiac output on the blood flow velocity in the middle cerebral artery was measured using transcranial Doppler sonography (TCD). RESULTS: Under the hypervolemic hemodilution supported with dopamine/dobutamine a dosage-dependent increase of 12% in blood pressure and a 53% increase in cardiac output was observed. In the affected hemisphere, flow velocity was one fourth lower (significance p < 0.05) than in the unaffected hemisphere. With therapy, the systolic flow velocity was increased in the unaffected hemisphere by 27%, on the side of the lesion only 11%. Mean flow velocity remained nearly constant. The pulsatility index (PI) increased simultaneously by 46% in the affected and 47% in the unaffected hemisphere. CONCLUSION: Similar effects on TCD-flow velocity and PI under comparable slight increases in blood pressure are not known. The increase in cerebrovascular resistance can be ascribed to a counter-regulation of the cerebral autoregulation, triggered by an increase of cardiac output.

Aged↗
PubMed1996

Influence of intravascular molecular weight of hydroxyethyl starch on platelets.

Complications concerning the blood coagulation have been observed repeatedly after administration of highly substituted, high molecular weight hydroxyethyl starch (HES), but it has not been examined as to how intravascular molecular weight and degree of substitution of HES influence platelet number and volume after repeated administration. Thirty patients with cerebrovascular diseases were treated for 10 days with hemodilution. 500 to 1500 ml of HES 200/0.62(n=10), HES 200/0.5(n=10) or HES 40/0.5(n=10) were infused daily. During the first days, the number of platelets was not lowered beyond the dilution effect, but at the end of the therapy the number of platelets had increased in all 3 groups beyond the initial value. Platelet volume was lowered significantly in the 3 groups. HES 200/0.62 caused the largest drop in platelet volume (-10%, p<0.01). A possible explanation could be that HES macromolecules are attached to platelets or are phagocytized by them. The larger platelets are then broken down and, to compensate the loss, more thrombocytes are released. A correlation between the molecular weight of HES and the breakdown rate of the platelets can be suspected, because HES 200/0.62 has the highest intravascular mean molecular weight(121 kD) and the largest effect on platelet volume.

Blood Platelets↗
PubMed1996

Decrease of fibronectin following repeated infusion of highly substituted hydroxyethyl starch.

OBJECTIVE: Fibronectin (Fn) plays an important part in unspecific defense mechanisms because of its ability to mediate the binding of foreign-body particles, bacteria, collagen, and other macromolecules to phagocytising cells of the reticulo-endothelial system (RES). The aim of the present study was to examine the effect of a 10-day hemodilution therapy on Fn concentration in humans. DESIGN: The patients were randomized and treated with either 10% hydroxyethyl starch (HES) 200/0.62 or 6% HES 200/0.62. SETTING: Neurology department of an university clinic. PATIENTS: We examined 12 patients with cerebrovascular perfusion disturbances. INTERVENTIONS: The Fn concentration was determined using simple radial immunodiffusion. RESULTS: The Fn concentration dropped significantly in all 12 patients (p < 0.01) in a dose-dependent manner beyond the dilution effect. 10% HES 200/0.62 caused a Fn decrease from 26.6 +/- 9.2 to 10.0 +/- 2.2 mg/dl (-62.2%), 6% HES reduced Fn from 25.5 +/- 9.9 to 15.0 +/- 3.2 mg/dl (-41.1%). In one patient there was a continuous decrease of Fn from 41.0 down to only 6.4 mg/dl. CONCLUSION: According to the results of animal experiments, the decrease of Fn seems to indicate depression of the RES. Besides its defense function, Fn probably plays a role in embryogenesis, wound healing, and blood clotting. Therefore, we assume that the drug-induced reduction of Fn possibly has clinical relevance.

Animals↗
PubMed1996

High-velocity bullet causing indirect trauma to the brain and symptomatic epilepsy.

Epilepsy is a frequent consequence after missile wounds of the brain. So far, no epilepsy cases with missile injury have been described in which epilepsy ensued without direct missile injury of the brain. During World War II, in 1941, our patient, then a soldier in the German army, suffered a bullet injury to the head; the bullet entered the cranium at the base of the nose. The bullet penetrated the head below the base of the cranium and remained stuck subcutaneously left of the second cervical vertebra. In the field hospital the patient suffered from focal seizures. The fits ceased within a few years under medication. In 1990 the seizures returned, this time with secondary generalization. In our case, a 7.62-mm bullet from the Russian Tokarev military pistol was used, which is known to have the highest muzzle velocity of all handguns available (> 500 m per second). We suspect that the so-called hydrodynamic effect of this high-velocity bullet caused an indirect trauma to the brain. This case shows that symptomatic epilepsy can occur after a penetrating head injury, without direct injury to brain tissue by a missile. High-velocity missiles are increasingly used in armed conflicts around the world. In light of the case reported here, in which the initial epilepsy was exacerbated more than 50 years after the wounding event, physicians must consider this possibility when dealing with veterans presenting with seizures. This case also has implications for the payment of benefits and pensions.

Adult↗
PubMed1996

[Decrease of thrombocyte volume after several days infusion of highly substituted medium molecular weight hydroxyethyl starch (HAES 200/0.62)].

Dextrans are known to inhibit platelet aggregation. However, conflicting results have been reported with hydroxyethyl starch (HES), usually administered as a single dose. To clarify this, we studied the effects of HES on platelet number, aggregation and volume during the course of long-term hemodilution therapy. Twelve patients with disturbances of cerebrovascular perfusion were randomized and divided into two groups of 6 patients each. One group was treated with 10% HES 200/0.62, the other with 6% HES 200/0.62. The patients in group 1 received a loading dose of 500 ml, followed by 500 ml daily for 10 days. Group 2 patients were infused a loading dose of 500 ml, followed by 1000 ml on days 1 to 4 and 500 ml on days 5 to 10. 10% HES had a larger volume effect. The hematocrit was lowered by 19.0%, whereas 6% HES caused a decrease of only 15.6%. 10% HES lowered the platelet number significantly (p < 0.05) by 5.8%, 6% HES did not lower the platelet number significantly. Platelet volume decreased significantly during therapy (p < 0.05) in both groups. 10% HES reduced the platelet volume by 13.9%, the reduction with 6% HES was 9.0%. Under therapy with 10% HES, platelet aggregation declined slightly, but significantly (p < 0.05), whilst no effect was seen with 6% HES. During long-term hemodilution therapy with HES, the initial decrease in platelet number, which is due to dilution, is quickly compensated. The continuous decline in mean platelet volume during therapy is probably due to colloid-osmotic shrinkage. Since there is a positive correlation between platelet size and function, the slight inhibition of platelet aggregation caused by 10% HES is possibly due to the observed decline in platelet volume.

Blood Platelets↗
PubMed1996

[Cerebral infarct in chronic acetylsalicylic acid poisoning].

Salicylates increase the risk of hemorrhage. An ischemic brain infarct has not previously been described following intoxication with salicylates. Case report. A 58-year-old comatose patient was admitted with symptoms of a basilar artery thrombosis. A diagnostic angiography was impossible because laboratory results showed a prothrombin time (Quick) of 9% and a toxic salicylate level of 528 mg/l. During the next few days CCT and MRI scans revealed ischemic infarctions within the brain stem. Discussion. Salicylates can induce hemorrhage both by inhibiting platelet aggregation and - especially in higher doses - by vitamin K antagonism, leading to severe coagulopathy. The occurrence of an ischemic infarction, as presented in this case report, can be explained by a reduction of the vitamin K-dependent protein C level.

Aspirin↗
PubMed1996

Influence of low and medium molecular weight hydroxyethyl starch on platelets during a long-term hemodilution in patients with cerebrovascular diseases.

It is a well-known fact that plasma substitutes reduce the number of platelets after one-time administration due to a dilution effect. So far, it has not been sufficiently investigated how a long-term hemodilution therapy affects platelet number, volume distribution and function. In 20 patients with cerebrovascular diseases a 10-day hemodilution therapy was carried out. The patients were randomly and double-blind treated with either medium molecular weight (MMW) hydroxyethyl starch (HES) 200/0.5 or low molecular weight (LMW) HES 40/0.5. On the first day of therapy, both groups showed a significant reduction in the number of platelets (-13.2% and -8.4%, respectively, p < 0.05), which was smaller than the dilution effect. During the course of the therapy, the platelet number increased, reaching its initial value. Mean platelet volume decreased in both groups significantly (MMW HES -4.7%, p < 0.05, LMW HES -4.6%, p < 0.01). The share of large platelets decreased disproportionately (MMW HES -15.4%, p < 0.01, LMW HES -11.4%, p < 0.01). Spontaneous platelet aggregation was not affected by HES. During the course of a long-term hemodilution therapy, the initial dilution-induced drop in platelet number is quickly compensated. The decline in mean platelet volume, which increases towards the end of the therapy, is due to a great extent to a decline in the number of large platelets. This in turn is probably caused by a colloid-osmotic shrinkage of the platelets and increased degradation. There were no signs for a clinically relevant impairment of platelet function.

Blood Platelets↗
PubMed1995

HES 200/0.5 is not HES 200/0.5. Influence of the C2/C6 hydroxyethylation ratio of hydroxyethyl starch (HES) on hemorheology, coagulation and elimination kinetics.

The plasma clearance of hydroxyethyl starch (HES) depends on the initial molecular weight and the degree of substitution. So far, little attention has been paid to the clinical relevance of the C2/C6 substitution ratio of hydroxyethyl starch. 10 patients with cerebrovascular circulatory disturbance received hemodilution therapy for 10 days, consisting of 10% HES 200/0.5 (mean molecular weight 200 kD, degree of substitution 0.5) with a C2/C6 ratio of 13.4. A second group of 10 patients received a starch solution with identical initial molecular weight and degree of substitution but with a C2/C6 ratio of 5.7. After the administration of a single dose, no significant differences between the two groups were observed. After repeated administration, significant differences could be detected in hemorheology, coagulation and elimination (p < 0.01). The larger C2/C6 ratio led to a higher intravascular mean molecular weight (95 vs. 84 kD), which in turn led to a higher increase in serum concentration during the therapy (14.7 vs. 8.6 mg/ml). Hematocrit was lowered more (-30.5 vs. -23.5%) and plasma viscosity was increased more. There was also a more pronounced increase in partial thromboplastin time (+30% vs. +13%) and a factor of 2 larger decrease of factor VIII/von Willebrand factor-complex (p < 0.01), which exceeded the dilution effect. The higher C2/C6 ratio of HES 200/0.5/13.4 slows down enzymatic degradation. After repeated administration of this starch, large molecules accumulate which are inefficiently degraded. The same effect has been observed after therapy with highly-substituted HES. This accumulation of large molecules leads to a beneficial longer lasting volume effect. The disadvantages include an increase in plasma viscosity and coagulation disturbances, which cannot be explained with the respective dilution effect alone. For these reasons, the C2/C6 ratio is of clinical relevance and should be included in the product labeling in the future.

Alkylation↗