Monitoring of oral anticoagulation by an amidolytic factor X assay. A long-term study in 42 patients.

The validity of the amidolytic Factor X assay for the control of long term oral anticoagulation (OA) was investigated in 42 patients randomized into 2 groups; PT group (anticoagulant dosage according to PT) and F.X group (anticoagulant dosage based on F.X). An independent expert's dosage according to F.X served for analysis in the former group. In the F.X group the F.X based dosage was considered valid only when not differing by more than 15% from the expert's PT based dosage. Confirming the good correlation between PT and F.X the study further demonstrates that the changes from one control to the next one, delta PT and delta F.X, too, are significantly correlated (r = 0.58, p less than 0.001, n = 217). In over one third of the periods the dosage proposals based on PT and F.X were identical and differed by more than 15% in only 12/217 instances. Our results justify a large trial on the control of OA by the amidolytic F.X assay.

Sequential treatment of arterial occlusions with porcine plasmin and low dose streptokinase.

Sequential treatment of arterial occlusions of the leg with porcine plasmin and low dose streptokinase results in a strong systemic proteolysis as already seen in deep leg vein thrombosis. In 31 of 45 patients the blood flow through major arterial segments could be restored. Thrombolytic success is possible within the first two treatment days but for the majority of the cases fibrinolytic therapy for 3-6 days is needed. On the average treatment was 1 day shorter than in DVT cases. No statistical relationship between local thrombolysis and systemic proteolysis was detected. The thrombolytic efficacy of this regimen compares favourably with earlier experience on fibrinolytic therapy in arterial occlusions.

Sequential treatment of deep leg vein thrombosis with porcine plasmin and low dose streptokinase.

Sequential treatment of deep leg vein thrombosis with porcine plasmin and low dose streptokinase (10,000-20,000 U/h) produces strong systemic fibrinolysis as demonstrated by the sustained decrease of euglobulin lysis time, of thromboplastin time values in percent, fibrinogen and factor V levels. There is a statistically significant negative correlation between thrombolytic results and euglobulin lysis time. Treatment period below 3 days are unlikely to give satisfactory results. Occluded vein segments with an apparent median age of 4 days including thrombi older than 10 days (20% of cases) are cleared with an average chance of 50%. Complete dissolution of all thrombi proximal to the crural veins has been demonstrated in 47/114 = 41.2%, some thrombolytic effects in 31/114 = 27.2% and treatment failure in 36/114 = 31.6%. The data favour laboratory monitoring of thrombolytic therapy.

Side effects of thrombolytic treatment with porcine plasmin and low dose streptokinase.

In the sequential thrombolytic therapy with porcine plasmin and low dose streptokinase side effects are mainly due to bleeding, intolerance reactions are less important. Treatment had to be prematurely stopped in 42 (37%) of 114 DVT cases because of severe bleeding and in 12 (10%) due to intolerance reactions. The corresponding figures for the 45 cases with arterial occlusions are 15 (33%) and 2 (4%) respectively. The intensity of systemic proteolysis as represented by the thromboplastin time is significantly correlated with haemorrhagic manifestations. Macrohematuria and bleeding from puncture sites are the most frequent haemorrhagic complications followed by spontaneous bleeding into skin and muscles. Non-fatal intracranial bleeding occurred in 1 DVT case (0.9%) and in 2 patients with arterial occlusions (4.4%). The benefit of this potent thrombolytic regimen would greatly improve if a strong reduction of premature treatment stop could be achieved.

Monitoring of heparin treatment. Comparison of thrombin time, activated partial thromboplastin time, and plasma heparin concentration, and analysis of the behavior of antithrombin III.

Three laboratory methods for monitoring heparin treatment have been compared using 63 plasma samples: the thrombin time, the activated partial thromboplastin time, and the measurement of the heparin concentration using a chromogenic substrate. A good correlation was found between the methods. However, the intensity of anticoagulation was identical in only 27 of the 63 samples (43%) when the thrombin time and the activated partial thromboplastin time were compared. Fully discordant results were recorded for four samples (6%). The thrombin time was found to be more closely related to the plasma heparin concentration than was the activated partial thromboplastin time. Both antithrombin-III activity and immunologic levels were lower in the group with strong heparinization. It is suggested that the thrombin time is a good and safe method for monitoring heparin treatment.

Assessment of collateral perfusion: a pharmacodynamic study with buflomedil hydrochloride.

The aim of the study was to assess the influence of Buflomedil hydrochloride on collateral function. Ten patients with isolated superficial femoral occlusions were investigated twice by duplex sonography with measurement sites at the common femoral artery (CF) and the popliteal artery (PA). After the second scan 200 mg of Buflomedil hydrochloride were infused; the infusion was followed by a third duplex examination. Endpoints assessed included the arterial diameter (D(CF), D(PA)), the systolic peak velocity (Vmax), the mean velocity of the maximum envelope (Vmean m.e.), the intensity weighted time average mean velocity (Vmean i.w.), the maximum reverse flow velocity (Vrev), the end-diastolic velocity (Venddiast), the calculated volume flow (Q), the pulsatility and the resistance indices (PI, RI), and PI and RI based segmental damping factors (DF(PI), DF(RI)). For the CF measurement site the infusion of Buflomedil hydrochloride resulted in a significant reduction in Vrev and PI (p<0.05), whereas trends in the opposite direction (increase) were observed for both measures of Vmean and for Q (0.1

[Duplex sonography of the popliteal vein using physiologic conditions and following intravenous administration of dihydroergotamine]. / Duplex-Sonographie der Vena poplitea unter physiologischen Bedingungen und nach intravenöser Gabe von Dihydroergotamin (DHE).

Accurate assessment of blood flow velocities and diameter measurements in veins are possible by duplex-scanning. We used the technique for the measurement of venous blood flow velocity under different physiological conditions and after the administration of dihydroergotamine (DHE). In 15 healthy subjects (mean age 30.4 years) diameter, peak and mean flow velocity of the popliteal vein were measured in lying and standing position before and after intravenous administration of 1 mg DHE. Mean diameter of the popliteal vein was 0.62 +/- 0.06 cm in the recumbent position and was significantly larger in the erect position (0.84 +/- 0.1 cm). Peak flow velocity was 17.4 +/- 4.9 cm/s, mean flow velocity 6.0 +/- 2.4 cm/s in the recumbent subjects. There was a significant decrease (p less than 0.001) of both velocity parameters in erect position. DHE causes a significant (p less than 0.001) decrease in diameter of the popliteal vein (14.5%) at rest and the enlargement was less (p less than 0.001) marked when the subject got up. After DHE administration a statistically insignificant increase in peak and mean flow velocity at rest and a significant (p less than 0.001) increase in mean flow velocity in the upright position was observed. In addition DHE induced a more pulsatile venous flow. This finding may be of importance in the prevention of deep vein thrombosis. Our results show that duplex-scanning allows precise assessment of venous blood flow velocities under different conditions. The technique is useful for direct measurement of the efficacy of vein active drugs.

[Normal kidney function of the transplanted kidney in ipsilateral pelvic artery occlusion 15 years after transplantation. A case report]. / Normale Transplantatnierenfunktion bei ipsilateralem Beckenarterienverschluss 15 Jahre nach Transplantation. Ein Fallbericht.

A case of a 61-year-old women 15 years after right-sided renal transplantation is discussed. She suffered from rest pain in her right leg. Examinations revealed an occlusion of the right common iliac artery without signs of renal dysfunction or severe hypertension. After performing a extraanatomic femoro-femoral crossover bypass the patient had improved leg perfusion without a change in renal function.

[Late sequelae of deep venous thrombosis: a 13-year follow-up of 223 patients]. / Spätfolgen der tiefen Venenthrombose: ein 13-Jahres Follow-up von 223 Patienten.

To investigate late sequelae of deep vein thrombosis, 223 consecutive patients, 148 men, 75 women, aged 61.5 +/- 14.7 years, with phlebographically documented unilateral deep vein thrombosis were reexamined 13 years after the acute event. 29 had an isolated calf vein thrombosis, 45 a 2-level- (calf an popliteal), 72 a 3-level- (calf, popliteal and femoral), 62 a 4-level- (calf, popliteal, femoral and pelvic) thrombosis and 15 had a special location, for example an isolated popliteal or pelvic involvement. In the acute stage all patients were given full dose heparin followed by a six month period of oral anticoagulation. 144 were initially treated by thrombolytic treatment with streptokinase. Control phlebography 5-14 days after the onset of the treatment revealed no clearance in a so called negative group of 123 patients, aged 63.5 +/- 14.9 years, namely the 79 "only" anticoagulated and 44 unsuccessfully thrombolysed. In this negative group natural course of deep vein thrombosis can be studied. The positive group, comprising 100 patients, aged 59.4 +/- 13.9 years (25 with complete and 75 with partial lysis, after streptokinase), is compared with the negative group. The global incidence of postthrombotic syndrome in the natural course, 13 years after deep vein thrombosis, was 39%, 9.8% with and 29.2% without ulcer. Slight changes were noted in 25% and no change in 36%. The incidence of postthrombotic syndrome was correlated with the extent of the original thrombosis: 3.7% after isolated calf vein thrombosis vs. 55.2% after 4-level thrombosis. Moreover, the mortality after deep vein thrombosis and the frequency of recurrence in the interval and of venous symptoms were also correlated to the extent of the thrombosis. The incidence of post phlebitic syndrome in the positive group is significantly lower in patients with 3- and 4-level thrombosis (p = 0.01). Patients with complete and partial lysis also have less venous symptoms (for 3- and 4-level thrombosis p < 0.0001). Thus, the successful thrombolysis seems to be beneficial in long terms for patients with extended thrombosis. Therefore, in our hospital thrombolytic treatment is offered as an additional treatment to anticoagulation to patients with recent, less than 7 days old, 3- and 4-level-thrombosis without contraindications.

[Characteristic contributions of the venous duplex exam]. / Quelques apports particuliers de l'examen duplex veineux.

The major advantage of non invasive duplex scanning is the ability to combine its imaging capability (information on the morphology) with the possibility to detect Doppler spectra (hemodynamic information) of the visualised segment. This new method, mainly used for the investigation of arterial diseases, is more and more applied in phlebology too. The technique is very reliable in the diagnosis of deep vein thrombosis and in the investigation of varicose veins and their junctions with the deep venous system. In these indications duplex scanning is likely to become a standard technique. The use of duplex in phlebology, however, should not be limited to these indications. In this paper the results of some special phlebologic duplex studies are presented: A) changes in the subclavian vein induced by pace maker electrodes; B) utility in the differential diagnosis of deep vein thrombosis; C) efficacy in the control of caval filter; D) measurements of physiologic venous hemodynamics and quantification of phlebologic drug effects.

[Sexually and drug-stimulated erections are proportional]. / Sexuell- und pharmakostimulierte Erektionen sind proportional.

Even complex diagnostic tests may not establish aetiology and degree of erectile dysfunction (ED) in many patients. Therefore, we evaluated a self-report method with a restrictive focus to quality of erections which may yield information sufficient to make an aetiologic diagnosis. We studied 74 patients 25 to 75 years of age with untreated ED. Sexually stimulated erections were quantified and compared to duplexsonographically and clinically evaluated data from pharmacostimulated erections. Patients reported that there was a marked decrease in ability to penetrate the partner, to sustain an erection and of penile rigidity (p < 0.001). Parameters from duplexsonography and clinically assessed response to pharmacostimulation correlated (r = 0.72). Direct comparison of these data with quantified history showed no relation (r = 0.05). Using change in penile volume due to erection as a basis to compare with, showed significant correlation with quantified data from history (r = 0.26-0.34; p < 0.03) and measured parameters from pharmacostimulated erections (r = 0.44-0.55; p < 0.0001). Sexually- and pharmacostimulated erections are proportional to change in penile volume. Although there is a relation between erections emerging from both stimulations, quantifying history on sexually stimulated erections does not qualify to make an aetiologic diagnosis without using complex tests.

[Assessment of the leg veins using duplex ultrasonography]. / Abklärung der Beinvenen mit Duplexultraschall.

Duplex scanning, first used for the investigation of arterial diseases, is characterized by the combination of B-Mode ultrasound and spectral analysis or color imaging of PW-Doppler signals. This provides information on both the morphology of the vessel and the corresponding hemodynamics. Compared to the conventional noninvasive techniques in phlebology such as plethysmography and CW-Doppler its major advantage is the additional morphologic information. Until now this anatomical information was only available by invasive phlebography. This technique, however, gives only limited informations on hemodynamics. Using an appropriate technique of duplex scanning, the deep veins from the calf to V. cava as well as the superficial veins and the perforators can be examined. In the hand of a skilled investigator deep vein thrombosis can be diagnosed with accuracy. Compared to the gold standard phlebography sensitivity and specificity are high: 96% and 99% resp. The duplex technique is also very reliable in differentiating the diagnosis of deep vein thrombosis: Baker's cysts, hematomas and tumors usually are easily detected by B-scan. Investigation of chronic venous insufficiency is also possible by duplex-scanning. Imaging of the veins and pulsed Doppler analysis allows to determine whether the reflux is in the deep or superficial system. On a more scientific field duplex allows the precise noninvasive determination of hemodynamic parameters. Thus it is possible to measure physiologic venous hemodynamics and to quantify drug effectiveness. Duplex sonography holds a key position in the phlebological diagnostic procedure. This new technique causes no harm to the patient and important information is obtained at relative low costs.

[Diagnosis using ultrasound in peripheral arterial disorders: possibilities and limitations]. / Diagnostik mittels Ultraschall bei peripherer arterieller Durchblutungsstörung: Möglichkeiten und Grenzen.

Ultrasound plays an increasingly important role in investigating peripheral vascular disease. Two major approaches, the Doppler technique and the (B-mode) imaging technique, are routinely used. Duplex scanning combines the two ultrasonic techniques taking advantage of both the hemodynamic and anatomic data that can be obtained. The simple conventional Doppler devices may be used to measure limb blood pressure at rest and after exercise and to assess velocity patterns. Recent advances in duplex technology allow non-invasive assessment of the vascular tree from the aorta to below the knee. Compared with arteriography duplex scanning has a sensitivity of 96% and a specificity of 81%. In selected cases duplex scanning can safely and reliably replace arteriography.

[Ambulatory therapy in varicose veins]. / Die ambulante Therapie der Varikose.

The treatment of varicose veins comprises conservative and active options. Every patient with varices has to be informed on the conservative modalities and should apply them in daily life. Compression therapy, as the most important part of the conservative treatment, should be considered individually for any patient according to the varicose-type, the grade of chronic venous insufficiency and the compliance of the patient. Active treatment modalities are clearly indicated in varices with complications such as trophic skin changes, varicophlebitis or when varices cause pain. But the cosmetic problem should not be underestimated. Morphologic and hemodynamic information obtained by noninvasive duplex technique allows the individualization of the surgical strategy for each patient. Besides surgical techniques used being less and less traumatic (invagination stripping, stab evulsion phlebectomy), more and more interventions are realized under ambulatory conditions in local anesthesia, even crossectomy with partial stripping of truncal varices. More important and complex operations, interventions involving more than one saphenous vein or reinterventions in recurrent varices are still performed under hospital conditions. They require only a short hospitalization time (2 to 4 days). Considering this very favourable evolution in surgery with a net trend to ambulatory, thus more economic treatment, the indications for sclerotherapy--a traditionally ambulatory modality with high recurrence-rate--are limited to reticular varices and telangiectasies.

[Current trends in the treatment of deep venous thrombosis]. / Neue Trends in der Behandlung der tiefen Venenthrombose.

The therapeutic procedure in established deep venous thrombosis (DVT) is summarized. Proximal (2 to 4 levels), symptomatic, recent DVT of less than three weeks duration is still treated in the clinic. The patient receives heparin intravenously, 5000 IU as initial bolus and subsequently 25,000-30,000 IU (approximately 400 IU per kilo bodyweight)/24 hours as continuous infusion or, in particular cases, 15,000 to 20,000 IU subcutaneously two times in 24 hours). Oral anticoagulation is started on the 1st day. Mobilisation takes place when symptoms regress, usually after 2-3 days. If further studies with low molecular weight heparins (LMH) confirm the good efficacy and tolerance, these compounds could replace heparin-schemes by a single daily subcutaneous injection. Also admitted to the hospital institution are patients with DVT and suspicion of pulmonary embolism and patients in whom fibrinolysis or thrombectomy are considered. The less expensive induction of anticoagulation on an outpatient basis and the subsequent follow-up treatment is in our opinion justified in patients with distal DVT (1-2 levels), older proximal DVT (and superficial venous thrombosis reaching the deep vein) and in patients with a thrombosed subclavian vein.) These patients are mobilized immediately under 12,500 to 15,000 IU heparin b.i.d. administered subcutaneously or alternatively injection of LMH's s.c. once per day (200 anti Xa-units/kg), changing over rapidly to p.o. vitamin K antagonists. For ambulatory patients LMH's may replace heparin for a single daily application if further studies confirm efficacy, this for mostly practical reasons. Long term anticoagulation by LMH could be ideal as for instance in pregnant patients.

Lack of diagnostic tools to prove erectile dysfunction: consequences for reimbursement?

PURPOSE: Oral medications for treatment of erectile dysfunction may drastically increase health care expenses. Therefore, reimbursement for treatment will be limited in many countries. Proof of erectile dysfunction on an individual basis may be required. We determine whether erectile dysfunction can be proved by pharmacostimulation tests. MATERIALS AND METHODS: We prospectively evaluated 77 consecutive patients with a median age of 54 years (range 25 to 75) who presented with previously untreated erectile dysfunction. Assessment included patient reported semiquantitative data on sexual erections (rigidity, ability for vaginal intromission, duration), standard clinical and laboratory tests, and intracavernous injection test and color duplex sonography with 10 microg. intracavernous prostaglandin E1. Data were compared on the basis of the most important complaint, namely whether vaginal intromission was impossible, feasible only with manual assistance or possible but not long enough for satisfactory sexual performance. RESULTS: Of the 77 patients 36 (47%) were unable to perform vaginal intromission, 28 (37%) needed manual help and 13 (17%) had erections sufficient for penetration but were not satisfied with sexual performance. Patient reports were reliable as shown by the significant correlation of items (r = 0.77) and significant discriminating power among categories for penetration (analysis of variance p <0.001). In contrast, clinical response to intracavernous pharmacostimulation and flow parameters assessed by color duplex sonography could not discriminate among the groups. CONCLUSIONS: Erectile dysfunction could not be defined by pharmacostimulated erections but relevant erectile dysfunction was honestly reported. New and reliable tests for clinical assessment are required to support the application for reimbursement of treatment expenses for erectile dysfunction.

[Aneurysma spurium following arterial catheterization: diagnosis and follow-up]. / Aneurysma spurium nach arterieller Katheterisierung: Diagnose und Verlaufskontrolle.

Pseudoaneurysm (PA) formation is one possible complication after intra-arterial catheterisation. Due to danger of rupture PA must be clearly differentiated from haematoma. PA is an arterially perfused cavity near the puncture site with direct communication with the femoral artery. Its clinical diagnosis is unreliable. We systematically reviewed 628 patients who had undergone femoral catheterisation (for angiography, PTA, local thrombolysis or aspiration) over a period of 1 year. Duplex scanning was performed within 1 to 3 days after puncture in the cases with the slightest suspicion of PA. In 7 patients (1.1%) PA could be confirmed (2 after angiography, 3 after PTA and 2 after local lysis). On the ultrasound B-mode image PA appears as a low or anechoic structure which can be precisely measured. With pulsed (colour) Doppler, flow can be detected within a PA, allowing easy differentiation from thrombosed PA or from haematoma. The velocity of the systolic inflow-jet as well as of the diastolic outflow can be determined. The velocity of the inflow-jet will usually be much higher than the blood flow velocity in the femoral artery. Duplex-scanning allows repeated non-invasive follow-up examinations for better determination of indications for surgery. Of the 7 diagnosed PA, 2 needed prompt operation (1 because of rupture, 1 because of intense local pain). One patient required operation during follow-up because of increase in size of PA. In the remaining 4 patients, spontaneous thrombosis was observed with repeated duplex examinations.

[The incidence of post-thrombotic syndrome]. / Zur Häufigkeit des postthrombotischen Syndroms.

To evaluate the clinical and socio-economic importance of the postthrombotic syndrome (PTS), the following epidemiologic parameters are to be known: The incidence of deep vein thrombosis (DVT) in the population, the incidence of PTS after DVT, the prevalence of the PTS, the socio-medical consequences and the mortality. The DVT-incidence in the literature is about 3/1000 per year in the adult population. In our own follow-up study we found a global PTS-incidence of 40% (10% with, 30% without ulcer) 13 years after DVT. The PTS-incidence was correlated with the initial DTV-extent. The risk of PTS after 3- and 4-level DVT is significantly reduced by a successful fibrinolysis in the acute stage (p = 0.01). The mortality of patients with PTS is 3 times higher than in the population. 4% of the patients with PTS get disabled. To our knowledge an adequate study with direct assessment of the PTS-prevalence does not exist, but the PTS-prevalence can be deduced from large epidemiologic studies, such as the Basel-Study, in which the global chronic venous insufficiency is assessed. It amounts in the adult population between 0.5 to 1% for the PTS with and 3 to 5% for the PTS without ulcer.

[Control of oral anticoagulation: comparison between Quick and colorimetric factor X determination in 107 patients]. / Kontrolle der oralen Antikoagulation: Vergleich zwischen Quick- und kolorimetrischer Faktor-X-Bestimmung bei 107 Patienten.

Since monitoring of oral anticoagulation (OA) by prothrombin time (PT) is a source of standardization difficulties, the authors have tested another approach. 107 patients under long term OA were monitored by both PT and a colorimetric factor X assay (in vitro activation of factor X with RVV and assessment of amidolytic activity towards S-2222). The PT values were between 10 and 34% (therapeutic range 15--25%), and factor X levels were between 10 and 44% (therapeutic range 16--24%). The correlation between the two methods was highly significant (r = 0.65, p less than 0.001). In 68% of the patients the two tests gave the same information (55 subjects were adequately, 16 insufficiently and 2 over-anticoagulated). For a slightly broader therapeutic range (PT 15--30%, corresponding to 16--28% factor X) concordant information was obtained in 82% of the patients. During stable OA, PT and factor X assay gave very similar information. An advantage of the latter method is the possibility of automation, while a disadvantage is its insensitivity to factor VII.