Laser Doppler flux measurement for the assessment of cutaneous microcirculatio--critical remarks.

Back scattered Laser Doppler (LD) signals are composed of two different individual signals. The number of the moving particles and the speed of the particles in the measured tissue volume determine the frequency shift and the band width of the Doppler signal. The dependence of the Laser Doppler flux on the number of scattering particles is highly nonlinear: at very low hematocrit and high speed the axial migration of the cells to the centre of the blood vessels is very strong, so that in these cases - because of the parabolic flow profile - the Doppler flux measurement overestimates the mean real blood flow (up to two- or three-fold). The opposite is the case when the hematocrit is very high, then the blood flow might be underestimated (due to the increased amounts of blood cells near the vessel wall). In addition, a very change in number of moving particles - as can occur during the postprandial phase or during therapy - can change the signal also at a constant cell number. Also, it must be mentioned that the LD signal possibly is not only reflected by moving blood cells in the different skin layers but also by blood cells flowing in tissues below the skin (particularly below atrophied skin areas of older patients) so that in such cases the LD Flux signal reflects not exclusively the skin blood flow. Therefore, LD flux at rest may still be within the normal range even in advanced states of disease, since the scattered light is sampled from a tissue volume which may contain also non-nutritive shunt vessels. This critical analysis of the LD signals of course shall not lead to an overall rejection of the application of laser Doppler systems. Actual progress only can, however, be obtained under the exact consideration of anatomical conditions, technical restrictions and when generalizations are avoided.

Bridging with enoxaparin using a half-therapeutic dose regimen: safety and efficacy.

BACKGROUND: Low molecular weight heparin is widely used during the interruption of long-term oral anticoagulation in patients undergoing surgery. The optimal dose is still a matter of debate. The 8th ACCP Guidelines primarily recommend therapeutic-dose or low-dose low molecular weight heparin after stratification of the thromboembolic risk. We investigated the efficacy and safety of a standardized bridging therapy with enoxaparin in a half-therapeutic dose in patients with a target INR of 2,0 to 3,0. PATIENTS AND METHODS: In our prospective registry we studied 198 consecutive patients receiving oral anticoagulant therapy with phenprocoumon and a planned surgery. Phenprocoumon was stopped 7 days before surgery and after reaching an INR less than 2,0 all patients received enoxaparin in a half-therapeutic dose (1 x 1 mg / kg body weight (bw)/day) until the day before surgery. Enoxaparin was continued with the same dose split into 2 x 0,5 mg / kg bw / day after the procedure. Phenprocoumon was resumed within day 1 to 14 after surgery depending on the bleeding risk as determined by the surgeon. All patients were followed up for 28 days after surgery. RESULTS: Major surgery was performed in 148 patients (75 %). 175 patients (88 % of the total) had an intermediate thromboembolic risk. On average, enoxaparin was administered for 19,5 days. One patient (0,5 %) experienced arterial thrombosis after surgery, and one patient (0,5 %) required a second surgical intervention due to severe bleeding. CONCLUSIONS: In patients receiving oral anticoagulant therapy with a target INR of 2,0-3,0 and at an intermediate risk of thromboembolic events who require interruption of oral anticoagulant therapy a half therapeutic dose of enoxaparin seems to be safe and effective for bridging.

Successful angiographic embolization of recurrent elbow and knee joint bleeds in seven patients with severe haemophilia.

In haemophilic joints with high-grade arthropathy, bleeds occur that do not respond to replacement therapy of the deficient coagulation factor. The reason may be pathologically reactive angiogenesis in chronic synovitis. Seven patients with severe haemophilia A or haemophilia B experienced recurrent massive bleeds of one elbow joint or knee joint in the absence of trauma. After initial application of factor VIII or IX (fVIII/fIX; 50 IU kg(-1) bodyweight), there was only slow and never complete relief of symptoms. Despite intensive secondary prophylaxis maintaining the plasma level of factor concentrate at minimum 50%, new massive bleeds at the same location occurred. Vascular bleeding was suspected. Angiography of the arteries was performed via the femoral artery. Vessels identified as potential bleeding sources were embolized with embolization fluid (ONYX) in eight joints (six elbow and two knee joints). Under low-dose prophylactic treatment (15 IU fVIII or fIX per kg bodyweight for three times per week), no recurrent severe bleed unresponsive to coagulation factor replacement occurred after a mean observation time of 16 months after embolization. The consumption of factor concentrate decreased to one-third of the amount consumed before embolization. In conclusion, angiographic embolization with a non-adhesive liquid embolic agent might be considered as a promising therapeutic and coagulation factor saving option in joint bleeds not responding to replacement of coagulation factor to normal levels.

Studies on travel-related thrombosis.

Due to increased long-distance travelling, travel-related thrombosis and its prevention are frequently discussed between patients and their doctors. There is now well accepted evidence that thromboembolic events can occur during or after long journeys, but despite a plethora of studies on the subject, still very little is known about the height of the absolute risk, the underlying triggering factors and, especially, about the efficacy of specific prophylactic methods. Therefore the recommendations for the prevention of travel-related thrombosis, developed and published by experts in this field, are necessarily based on the risk assessment of the individual traveller and the methods of prevention supported by the experience in medical patients.

Traveller's thrombosis: international consensus statement.

In 2001, consensus meetings on traveller's thrombosis were held in Vienna and Berlin. The results of these conferences were subsequently published in VASA 2002. In 2006 a follow-up conference was organized in Hall, Tirol, Austria, in order to review new and emerging data and to update the conclusions and recommendations of the 2001 meetings. Prior to the conference key papers from peer-reviewed journals were pre-circulated to all participants. The consensus group discussed the data and drafted an updated statement. Thereafter, the writing group summarised the results including the pre-circulated material and additional papers identified by a formal literature search up to December 2007. In this article current knowledge on the incidence, pathophysiology and prevention of traveller's thrombosis is summarised. The assessment of individual risk is described and recommendations for prevention of traveller's thrombosis are given, based upon the conclusions of the Hall Conference.

[Longterm treatment of POAD with anticoagulants and platelet inhibitors after endovascular procedures and vascular surgery: what is evidence based?]. / Nachbehandlung der pAVK nach Interventionen und Gefässchirurgie mit Antikoagulanzien und Thrombozytenfunktionshemmern. Was ist gesichert?

Platelet inhibitors and anticoagulants are used in the longterm treatment after successful infrainguinal bypass grafts as well as endovascular revascularisation procedures. However, evidence of the usefulness of these therapies is limited with respect to efficiency (patency rate, mortality) and safety (bleeding tendency) concerning these indications. Sufficient data are only available for acetylsalicylic acid treatment after implantation of prosthetic bypass grafts, the data basis for the use of antithrombotic medication in venous bypass grafts or following successful balloon angioplasty with or without stent implantation is, however, inconclusive. The recommendation for lifelong therapy with acetylsalicylic acid after infrainguinal bypass surgery and endovascular treatment is based mainly on the concept of prophylactic treatment of manifest atherosclerotic disease.

Cardiogenic embolism as the main cause of ischemic stroke in a city hospital: an interdisciplinary study.

BACKGROUND: It is essential to understand the pathogenesis of ischemic stroke to ensure rational acute therapy and secondary prevention. We wanted to know the distribution of pathogenesis in patients of a city hospital and the differences in risk factors, neurologic deficits, disability, and delay in clinical admittance. PATIENTS AND METHODS: During a period of one year, 222 patients (mean age 76.6 years; 59% women) with complete acute ischemic stroke were admitted and underwent complete clinical and diagnostic procedures: CCT/MRI; Doppler- and color-coded duplex and transcranial sonography; echocardiography; use of the NINCDS stroke scale and the Oxford disability scale; study of risk factors, and exploration of delay in admittance. RESULTS: The following percentages of etiologies were evident: 31% cardiogenic embolism (60% with atrial fibrillation), 13% microangiopathy, 9% macroangiopathy, 11% cerebellar or brain stem infarction, 18% more than one cause and 18% no cause found. The patients with cardiogenic embolism showed significantly the highest scores on the stroke scale and the disability scale and had the shortest delay in admittance (57% were admitted within 3 hours). CONCLUSIONS: In a city hospital, cardiogenic embolism is the main cause of ischemic stroke. These patients suffer significantly the most severe neurologic deficits, dependence, and requirement of daily nursing care. These patients have the shortest delay in clinical admittance and the best chance of benefitting from acute therapy and early secondary prevention.

Treatment of acute ischemic stroke with the low-molecular-weight heparin certoparin: results of the TOPAS trial. Therapy of Patients With Acute Stroke (TOPAS) Investigators.

BACKGROUND AND PURPOSE: To study the safety and efficacy of the low-molecular-weight heparin certoparin, we performed a randomized, double-blind, dose-finding multicenter trial in patients with acute ischemic stroke (Therapy of Patients With Acute Stroke [TOPAS]). METHODS: We randomized 404 patients to 4 treatment groups within 12 hours of stroke onset: 3000 U anti-factor Xa (aXa) certoparin once daily (treatment group 1); 3000 U aXa twice daily (group 2); 5000 U aXa twice daily (group 3); and 8000 U aXa twice daily (group 4). The primary efficacy variable was the proportion of patients reaching a favorable functional outcome (Barthel Index >/=90 points) at 3 months. CT was performed at trial entry, after 7 days, and on clinical deterioration. RESULTS: The proportion of patients with Barthel Index >/=90 was not different between treatment arms (61.5%, 60.8%, 63.3%, and 56.3% in the 4 groups, respectively; intent-to-treat population). European Stroke Scale scores improved in all treatment groups within the first 14 days to a similar extent. During the follow-up of 6 months, percentages of patients with recurrent stroke/transient ischemic attack were 11.0%, 5.9%, 9.7%, and 13.0% in the 4 groups, respectively. Overall mortality was only 7.4%. Two parenchymal cerebral hematomas and 1 extracranial bleeding episode occurred in treatment group 1 versus 1 and 0 in group 2, 2 and 0 in group 3, and 4 and 5 in group 4, respectively. During certoparin treatment, 1 deep vein thrombosis but no pulmonary embolism was observed. CONCLUSIONS: Dose increase of certoparin up to 8000 U aXa twice daily did not improve the functional outcome of patients with ischemic stroke. Severe bleeding tended to be more frequent in the highest dose group only.

[Economy class syndrome: fiction or fact?]. / Economy-Class-Syndrom: Fiktion oder Faktum?

Several reports about the occurrence of deep vein thrombosis and pulmonary embolism following long-distance flights have led to the term "economy class syndrome". The underlying hypothesis was that a long term immobilisation in narrow economy class chairs of modern jet aircraft plays an important role for the development of deep vein thrombosis. Studies in healthy volunteers during several simulated long distance flights and during an actual long-distance flight confirmed the swelling of the lower legs complained by many long distance passengers, however, failed to reveal relevant changes of hemorheological or hemostaseological parameters. From these investigations no increased risk for thromboembolic diseases during long distance flights for healthy volunteers could be derived. Since this may be completely different for patients with risk factors for thromboembolic diseases prophylactic measures (compression stockings, anticoagulation) might be necessary.

Economy class syndrome: rheology, fluid balance, and lower leg edema during a simulated 12-hour long distance flight.

In order to study pathological changes that might lead to deep vein thrombosis and pulmonary embolism in long-distance air travel passengers, 12 healthy volunteers were investigated during 4 simulated 12-h flights (day and night). The influence of repeated leg exercise was compared with constant sitting. Plasma viscosity, hematocrit, albumin, fluid balance, and lower leg swelling were measured. Rheological studies showed only circadian rhythm alterations. An average of 1150 ml fluid was retained, which correlated with an increase in body weight. The lower leg volume increase was significant, but not pathological. Periodic leg exercising showed no measurable preventive effects. These changes in healthy human volunteers are within physiological variations and are not sufficient to provide a definitive cause of venous thrombosis in healthy passengers. They do, however, suggest alterations produced by long-distance air travel that could intensify the risk of developing deep venous thrombosis in passengers with predisposing risk factors.

Muscle tissue PO2 during moderate altitude exposure in patients with peripheral arterial occlusive disease.

OBJECTIVES AND METHODS: In 10 patients with peripheral arterial occlusive disease (intermittent claudication) and in 10 healthy volunteers serving as controls, muscle tissue pO2, transcutaneous pO2, arterial pO2 and rheological parameters were measured before and during breathing (for 20 min) of an oxygen reduced gas mixture simulating an altitude of about 8500 feet (2600 m, approximately 116 mm Hg pO2). Oxygen pressure values were determined by means of a polarographic method according to Ehrly and Schroeder using atraumatic micro-pt-needle electrodes. RESULTS: Tissue oxygen tension in the tibialis anterior muscle of patients with peripheral arterial occlusive disease decreased significantly from 6.5 mm Hg to 2.4 mm Hg (medians). The pooled histograms were markedly shifted to hypoxic values. The controls showed a decrease from 20.8 to 12.2 mm Hg and a strong shift to the left. Transcutaneous pO2 measured in the diseased leg decreased from 53.4 +/- 11.6 to 36.1 +/- 9.3 mm Hg (controls 57.1 +/- 9.9 to 39.7 +/- 8.9 mm Hg), arterial pO2 decreased from 80.2 +/- 15.1 to 60.0 +/- 10.4 mm Hg (controls: 86.5 +/- 16.0 to 64.7 +/- 13.6 mm Hg) and pulsoximetrically determined O2-saturation from 95.0 +/- 2.5 to 90.0 +/- 5.5% (controls: 96.1 +/- 2 to 92.0 +/- 4.2%). CONCLUSIONS: Exposure of patients with intermittent claudication to moderate altitude led to a marked decrease of tissue pO2 values in the diseased legs without any evidence of clinical worsening, especially no rest pain. It may be discussed if rest pain in ischaemic legs is due to low pO2-values or to disturbed microcirculatory perfusion.

Noninvasive methods in the early detection of restenosis after percutaneous transluminal angioplasty in peripheral arteries.

In a prospective study, several noninvasive methods were evaluated in the early detection of restenosis after percutaneous transluminal angioplasty in peripheral arteries. Sensitivity and specificity of various noninvasive resting and exercise methods for the detection of restenosis were determined. It is concluded that noninvasive follow-up after percutaneous transluminal angioplasty in peripheral arteries requires exercise testing with determination of ankle-arm index or segmental arterial pulse oscillography for the early detection of restenosis.

Effect of erythropoietin treatment on tissue oxygenation in patients with severe transfusion dependent renal anaemia.

OBJECTIVES: Severe renal anaemia can now be effectively treated with recombinant human erythropoietin (rhEpo). To evaluate muscle tissue oxygenation in patients with severe renal anaemia and the effects of an rhEpo treatment, muscle tissue oxygen tensions were measured in 9 patients suffering from end stage renal disease with severe renal anaemia before and during rhEpo treatment. METHODS: Muscle tissue oxygen pressure (method according to Ehrly and Schroeder), transcutaneous oxygen pressure (tcpO2) (Radiometer, Copenhagen), haematocrit (micro haematocrit method), plasma viscosity (Ostwald capillary viscometer) and erythrocyte aggregation (method according to Ehrly and Schmitt) were determined before as well as 4, 8, and 24 weeks after onset of treatment with 80 U/kg body weight 3 times per week. RESULTS: Muscle tissue pO2 values before treatment were markedly diminished when compared with normals and showed a marked increase into the normal range parallel to the increase in haematocrit. tcpO2 values were in the upper normal range before treatment and did not show significant changes during treatment. Erythrocyte aggregation and plasma viscosity did also not show significant changes. CONCLUSION: During rhEpo treatment a marked increase of muscle tissue pO2 can be found. This increase may be one of the mechanisms responsible for the improved well being and physical exercise tolerance in these patients due to erythropoietin treatment.

Recanalization of chronic arterial occlusions: low-speed rotational angioplasty. 5 years experience in peripheral and coronary vessels.

Chronic complete occlusions still represent the major technical limitation of percutaneous transluminal angioplasty, both in peripheral and coronary vessels. The clinical use of low-speed rotational angioplasty started in 1986 for the peripheral and in 1987 for the coronary arteries, and has already become part of the clinical routine in several centres. Up to now more than 350 patients with peripheral and 250 patients with coronary occlusions have been treated in Frankfurt; a multicentre questionnaire already contains information about 1,252 patients with peripheral vessel obstructions. In peripheral occlusions the acute success rate was more than 80% if low speed rotational angioplasty was used as the first attempt; after failure of conventional techniques still more than 60% of the vessels could be recanalized successfully. In addition to occlusions of the arteries of the lower limb, indications now may include the iliac artery and the subclavian artery. In each of the patients with chronic coronary occlusions an attempt with conventional techniques had failed before. Following a learning curve, which was also influenced by a better understanding of morphological preconditions, the acute success has now reached 70%. Both in patients with peripheral and those with coronary occlusions the technique turned out to be a safe procedure. Early angiographically documented long-term results in both indications are comparable with conventional balloon techniques. It is concluded that the use of low-speed rotational angioplasty (ROTACS) can improve the results of non-operative invasive treatment, both in peripheral and in coronary arteries.

[An unusual cause of arterial vascular occlusion with peripheral embolism]. / Ungewöhnliche Ursache eines arteriellen Gefässverschlusses mit peripheren Embolien.

A 34-year-old man presented with a three week history of a bluish discolouration, tingling paraesthesia and severe intermittent pain of the right foot. Angiography showed occlusion of the right superficial femoral artery above the knee, as well as embolic occlusion of the distal lower limb. A fluoroscopic study demonstrated a tirefond perforating the femoral bone just on the level of the occlusion. Two osteosynthetic operations had been performed after a comminuted fracture seventeen and five months earlier, respectively. After the initial fibrinolytic therapy was without improvement over a period of 32 hours, the osteosynthetic screw was removed surgically. It was covered by callous tissue und protruded through the cortical layer more than 15 mm. After extraction of the screw and removal of thrombotic material the femoral artery was patent on control angiography.