E. Wenzel

Effects of garlic coated tablets in peripheral arterial occlusive disease

SummaryFor the first time, a weak clinical efficacy of a 12-week therapy with garlic powder (daily dose, 800 mg) is demonstrated in patients with peripheral arterial occlusive disease stage II. The increase in walking distance in the verum group by 46 m (from 161.0 ± 65.1 to 207.1 ± 85.0 m) was significantly higher (P<0.05) than in the placebo group (by 31 m, from 172.0 ± 60.9 to 203.1 ± 72.8). Both groups received physical therapy twice a week. The diastolic blood pressure, spontaneous thrombocyte aggregation, plasma viscosity, and cholesterol concentration also decreased significantly. Body weight was maintained. It is quite interesting that the garlic-specific increase in walking distance did not appear to occur until the 5th week of treatment, connected with a simultaneous decrease in spontaneous thrombocyte aggregation. Therefore, garlic may be an appropriate agent especially for the long-term treatment of an incipient intermittent claudication.

Highly Substituted Hydroxyethyl Starch (HES 200/0.62) Leads to Type-l von Willebrand Syndrome after Repeated Administration

Hydroxyethyl starch (HES) is a frequently used plasma substitute that is popular due to a high degree of therapeutic safety. However, the administration of large volumes of highly substituted, high-molecular-weight starch often leads to iatrogenic von Willebrand syndrome (vWS) with hemorrhagic complications. In patients with cerebral circulatory disturbances we carried out hemodilution therapy during 9-10 days, infusing HES 200/0.62. A von Willebrand factor (vWF) multimeric analysis was carried out in 6 patients using a modified western blot according to the sodium dodecyl sulfate agarose gel electrophoresis method. The vWF multimeric analysis showed that all multimers decreased to the same degree, corresponding to type-I vWS.

[Determination of reference ranges of rheologic parameters: study of 653 randomly selected probands of the Aachen district].

To determine reference ranges for rheologic parameters (hematocrit, plasma viscosity, erythrocyte aggregation, erythrocyte rigidity) a randomized study involving 653 subjects was carried out. Conditions of sampling, transportation and storing of blood specimens were established prior to the survey. Only 283 subjects met the criteria for enrollment in the study; the others were rejected because of inconspicuous history, normal findings in physical and Doppler-sonographic examination and absence of the risk factors hypertension, diabetes mellitus, overweight, rheumatic diseases, and smoking. The reference range for hematocrit was determined by an impedance-measuring device to equal 39-52% for males and 34-50% for females. The reference range for plasma viscosity, measured by a capillary-tube-plasma viscometer, was found to vary from 1.14 mPas to 1.34 mPas. The reference values for the standardized erythrocyte aggregation index was determined with the mini erythrocyte aggregometer to range from 8 to 21. Erythrocytes measured with the selecting-erythrocyte rigidometer showed a rigidity reference range between 0.83 and 1.19. Analysis of the results revealed that the parameters were independent of age (except in young children) and sex (with the exception of hematocrit).SummaryTo determine reference ranges for rheologic parameters (hematocrit, plasma viscosity, erythrocyte aggregation, erythrocyte rigidity) a randomized study involving 653 subjects was carried out. Conditions of sampling, transportation and storing of blood specimens were established prior to the survey. Only 283 subjects met the criteria for enrollment in the study; the others were rejected because of inconspicuous history, normal findings in physical and Doppler-sonographic examination and absence of the risk factors hypertension, diabetes mellitus, overweight, rheumatic diseases, and smoking.The reference range for hematocrit was determined by an impedance-measuring device to equal 39–52% for males and 34–50% for females. The reference range for plasma viscosity, measured by a capillary-tube-plasma viscometer, was found to vary from 1.14 mPas to 1.34 mPas. The reference values for the standardized erythrocyte aggregation index was determined with the mini erythrocyte aggregometer to range from 8 to 21. Erythrocytes measured with the selecting-erythrocyte rigidometer showed a rigidity reference range between 0.83 and 1.19. Analysis of the results revealed that the parameters were independent of age (except in young children) and sex (with the exception of hematocrit).

Gray platelet syndrome: selective α-granule deficiency and thrombocytopenia due to increased platelet turnover

SummaryClinical and laboratory studies of two siblings, both suffering from gray platelet syndrome (GPS) are described. The patients had a mild bleeding disorder, their platelets were blue-gray in panoptic stains, and α-granules were markedly reduced, as shown by electron microscopy. The platelet content of platelet factor 4 and that of β-thromboglobulin were significantly reduced (3%–7% of normal). Platelet count was decreased (33–150×109/l) and small platelets were increased in platelet volume distribution. Bleeding time was prolonged on most occasions. Bone marrow aspiration was performed in one patient and revealed increased reticulin fibers, however, megakaryocyte count was normal. The mean platelet survival was 4.8 days using 111indium-labelled platelets. In this patient, platelet-associated IgG was within the normal range. Prednisone therapy failed to increase platelet count. Dental surgery was performed under cover of desmopressin and no bleeding complication occurred; however, no improvement of bleeding time was observed. The patient delivered a healthy male infant without hemorrhaging while under concurrent platelet transfusion therapy.

Primary and secondary microcirculatory disorders in essential hypertension

SummaryIn this prospective cross-sectional study blood fluidity and peripheral microcirculation were measured in patients suffering from essential hypertension with and without macroangiopathy. The cutaneous microcirculation was evaluated by intravital microscopy and the intramuscular by pO2 needle electrode. Disorders in the microcirculation without macroangiopathy in the system of the feeding arteries are defined as primary microangiopathy. Disturbed microcirculation with macroangiopathy in the feeding arteries in one area but no detectable microcirculatory disorder in another region is defined as a secondary microcirculatory disorder. Of the 57 patients in this study 27 had a primary microcirculatory disorder. It was remarkable that all 27 hypertension patients had a microcirculatory disorder in the area of the skin. Intramuscular microcirculatory disorder on its own without affection of the skin was not detected in any case. An exclusively secondary microcirculatory disorder occurred in 16 patients. This study shows that 93% of the patients with long-term essential arterial hypertension have microcirculatory disorders. It is most interesting that about one-half of these hypertension patients had a primary microcirculatory disorder, i.e., no indication of a hemodynamically active stenosis was found in the large vessels.

Influence of Low Molecular Weight Hydroxyethyl Starch (HES 40/0.5-0.55) on Hemostasis and Hemorheology

Hydroxyethyl starch (HES) with a high or medium molecular weight (MW) and a high degree of substitution is difficult to degrade and leads to an accumulation of large molecules. These molecules have a negative effect on hemostasiological parameters. In 10 patients with cerebrovascular diseases, a hemodilution therapy was carried out with low MW HES for 10 days. Due to the low MW of the HES used (56-61 kD), the rheological parameters erythrocyte aggregation and plasma viscosity were significantly lowered (p < 0.01). No coagulation parameters studied were affected beyond the dilution effect, which was measured using the decline in hematocrit. Low MW starch is a volume substitute that is well-suited for repeated infusion or hemodilution therapy, particularly for patients with increased hemorrhagic diathesis, because it does not affect hemostasis. The disadvantage of a relatively short volume effect can be compensated through a continuous infusion of a larger volume.

Subcutaneous Injection of Desmopressin (DDAVP): Evaluation of a New, More Concentrated Preparation

A more concentrated desmopressin (DDAVP) preparation (40 micrograms/ml), which required small injection volumes (less than 1 ml), was studied in a double-blind trial in 10 healthy volunteers, 12 patients with haemophilia A, and 8 patients with uraemic bleeding. DDAVP was administered by subcutaneous injection at a dose of 0.4 micrograms/kg body weight. In healthy subjects, peak levels of DDAVP ranging from 480 to 638 pg/ml were reached 1 h after the subcutaneous injection and DDAVP was eliminated with a mean half-life of 3.1 h. DDAVP produced a 2.5-fold (3.0-fold) increase of factor VIII:C (factor VIII:Ag) and a 1.9-fold (2.2-fold) increase of von Willebrand factor:Ag (ristocetin cofactor) over baseline levels. Additionally, a 2.1-fold increase of tissue-type plasminogen activator antigen was observed. Factor VIII and von Willebrand factor were rapidly eliminated with a half-life ranging from 1.3 to 5.7 h and from 1.1 to 11.4 h, respectively. In haemophilia A patients, DDAVP produced a 2.3-fold increase of factor VIII:C 1 h after the injection. DDAVP was given on 8 occasions for management of bleeding, and only in 1 patient did a wound haematoma (after herniotomia) occur. In 7 of the 8 patients with uraemia the bleeding time shortened, and in all patients an increase of platelet retention and a decrease of platelet count was observed (p less than 0.05). No serious local or systemic untoward side effects were observed.

The use of heat-treated factor VIII-concentrates in von willebrand's disease

SummaryIn vitro investigations have demonstrated a high F VIII:Rcof potency and a high F VIII:Rcof/F VIII R:Ag ratio of two heat-treated F VIII concentrates. We therefore studied the in vivo effectiveness of these preparations (F VIII HSR, Behringwerke Marburg and F VIII HTR, Travenol) in five patients with von Willebrands disease (vWd). In the steady state in vivo recoveries of F VIII:Rcof ranged from 73–153% after transfusion of F VIII HSR and from 11.5–17% after F VIII HTR respectively. The gain of F VIII-complex after F VIII HS was comparable to cryopecipitate (KryobulinR SP, Immuno AG Wien). All three products shortened the bleeding-time. Three of our five patients underwent surgery (Billroth I, papillotomy, laparatomy, open heart surgery) under F VIII HS cover without bleeding complications. The dose applied ranged from 20 to 40 U/kg at 8 or 12 h intervals for a period of approx. 14 days. Serum-transaminase elevations were observed in two of four patients after F VIII HT treatment. Although the risk of hepatitis of heat-treated F VIII concentrates remains to be determined, these products proved to be effective in vWd. The major advantages of these preparations are stability, rapid solubility, a low content of contaminating proteins, and a rapid, general availability.

The subcutaneous administration of the vasopressin analogue 1-desamino-8-D-arginine vasopressin in patients with von Willebrand's disease and hemophilia

SummaryTwenty-one patients suffering from mild von Willebrands disease (vWd) and patients suffering from mild or moderate hemophilia A received 1-desamino-8-D-arginine vasopressin (DDAVP) (Minirin®, Ferring AG) s.c. at a dose of 0.4 µg/kg body weight. Additionally, two hemophiliacs and 22 patients with vWd received DDAVP i.v. Within the observation period of 3 h Factor (F) VIII:C levels increased 2.4 × baseline levels in hemophiliacs, and the maximal effect was observed 3 h post DDAVP s.c. In patients with vWd post DDAVP s.c. (i.v.) a 2.7 (3.4), 2.1 (1.9) and 2.2 (2.8) fold increase for F VIII: C, F VIIIR:Ag and F VIII:Rcof was observed. In eight patients suffering from vWd with additional F XII deficiency a small and transitory but significant increase of F XII levels was detected post DDAVP s.c. No local or systemic side effects were observed. In five patients with vWd tooth extractions were performed without bleeding complications under DDAVP s.c. treatment. Two patients practiced self-treatment by injecting the drug s.c. at home. We thus conclude that s.c. DDAVP is an effective, reliable, and cost-reducing form of treatment that does not bring with it the risk of transmitting infectious diseases in patients with vWd and hemophilia and that can be administered at home.

Capillary Microscopic and Rheological Dimensions for the Diagnosis of von Willebrand Disease in Comparison to other Haemorrhagic Diatheses

It is known that angiodysplasia influence macrocirculation as well as microcirculation in patients with vWD. In the present study it was examined if intravital capillary microscopic dimensions (morphologic and dynamic) in skin (nailfold) in combination with rheologic parameters could give indications for the presence of vWD in patients with haemorrhagic diathesis. Patients with vWD (n = 100; 92 type 1: definite type 1:78 and possible type 1:14: 8 type 2A) have in comparison to patients with other haemorrhagic diathesis [thrombocytopathy (n = 122), thrombocytopenia (n = 101). severe haemophilia A (n = 50) and severe haemophilia B (n = 20). congenital dysfibrinogenaemia (n = 22), oral anticoagulation with phenprocoumone (n = 112)] and to apparently healthy subjects (n = 100) a significantly increased capillary torquation (median index: 3.5), a venolar and an arteriolar capillary dilatation (median: 16.5 microm; median: 15.1 microm) and the highest part of microscopic bleedings (extravasates) with 40% in the video capillary microscopy as morphological changes. Only the congenital dysfibrinogenaemia appears with a larger dilatation in venolar capillaries (median: 14.5 microm). Microscopic bleedings are much less common in other haemorrhagic diatheses with a frequency between 4% and 13%. In the vWD a significantly reduced duration of reactive hyperaemia (median: 150 sec). This is the only dynamic change that can be taken as a possible hint for a loss of flexibility within the precapillary vessels. A significantly reduced plasma viscosity (< 1.25 mPas) is typical for the vWD due to the increase of the shear stress in blood plasma because of the reduction of vWF-activities. Changes of the capillary morphology (dilatation, extravasates, capillary torquation) and the hypoplasmaviscosity are most sensitive for the vWD (75%, 65%, 40%, 80%) with a fairly high specifity (up to 93%) and a positive predictive value of 99%. As a conclusion it seems reasonable to discuss the introduction of video capillary microscopy as a screening test for haemostasiological and angiological centers.