Association between P-selectin levels and left atrial blood stasis in patients with nonvalvular atrial fibrillation.

BACKGROUND: P-selectin - a biomarker of platelet and endothelial cell activation is elevated in patients with non-valvular atrial fibrillation (NVAF). However, the association between sP-selectin level and thromboembolic complications in NVAF patients remains controversial. We tested the hypothesis that plasma soluble P-selectin (sPSL) level correlates with the measures of left atrial blood stasis in NVAF. METHODS: Plasma sPSL concentration was measured using solid-phase ELISA in 103 NVAF patients (age 63 ±â€¯14 years; 26% women) and 48 normal sinus rhythm controls (NSR; age 64 ±â€¯14 years; 41% women) who were not on aspirin. Within the group of NVAF cases, 27 had no spontaneous echocardiographic contrast (SEC) detected by transesophageal echocardiography, 31had mild SEC, 15 moderate, 20 severe, and 10 patients had left atrial appendage thrombus (LAAT). RESULTS: The median soluble sPSL level was higher in NVAF cases compared to NSR controls [(interquartile range) 26 (20-32) ng/mL vs 22 (15-29) ng/mL, p = 0.0045]. Only NVAF patients with CHA2DS2-VASc score ≥ 1 had higher sPSL level compared to NSR controls. Patients with severe SEC had significantly higher sPSL levels [32 (24-38) ng/mL] compared to all other NVAF patients (p = 0.0042) and to NSR controls (p < 0.0001). Also NVAF patients with LAAT had higher sPSL level compared to NSR controls. CONCLUSIONS: There is a direct correlation between p-selectin level and severe blood stasis in the left atrium. Only NVAF patients with CHA2DS2-VASc score ≥ 1 or with LAAT had higher sPSL level compared to NSR controls.

Do incident and recurrent venous thromboembolism risks truly differ between heterozygous and homozygous Factor V Leiden carriers? A retrospective cohort study.

INTRODUCTION: While Factor V Leiden (F5 rs6025 A allele) is a known venous thromboembolism (VTE) risk factor, VTE risk among heterozygous vs. homozygous carriers is uncertain. MATERIALS AND METHODS: In a retrospective cohort study of Mayo Clinic patients referred for genotyping between 1996 and 2013, we tested Factor V Leiden genotype as a risk factor for incident and recurrent VTE. RESULTS: Among heterozygous (n=268) and homozygous (n=111) carriers, the prevalence of VTE was 54% and 68%, respectively (p=0.016). While mean patient age at first VTE event (43.9 vs. 42.9years; p=0.70) did not differ significantly, median VTE-free survival was modestly shorter for homozygous carriers (56.8 vs 59.5 years; p=0.04). Sixty-nine (48%) and 31 (42%) heterozygous and homozygous carriers had ≥1 VTE recurrence (p=0.42). In a multivariable model, idiopathic incident VTE and a second thrombophilia were associated with increased and anticoagulation duration >6months with reduced hazards of VTE recurrence; Factor V Leiden genotype was not an independent predictor of recurrence. CONCLUSIONS: Aside from a higher VTE prevalence and modestly reduced VTE-free survival, VTE penetrance and phenotype severity did not differ significantly among homozygous vs. heterozygous carriers, suggesting that VTE prophylaxis and management should not differ by Factor V Leiden genotype.

Cancer effect on periprocedural thromboembolism and bleeding in anticoagulated patients.

BACKGROUND: Patients with active cancer are often on chronic anticoagulation and frequently require interruption of this treatment for invasive procedures. The impact of cancer on periprocedural thromboembolism (TE) and major bleeding is not known. PATIENTS AND METHODS: Two thousand one hundred and eighty-two consecutive patients referred for periprocedural anticoagulation (2484 procedures) using a standardized protocol were followed forward in time to estimate the 3-month incidence of TE, major bleeding and survival stratified by anticoagulation indication. For each indication, we tested active cancer and bridging heparin therapy as potential predictors of TE and major bleeding. RESULTS: Compared with patients without cancer, active cancer patients (n=493) had more venous thromboembolism (VTE) complications (1.2% versus 0.2%; P=0.001), major bleeding (3.4% versus 1.7%; P=0.02) and reduced survival (95% versus 99%; P<0.001). Among active cancer patients, only those chronically anticoagulated for VTE had higher rates of periprocedural VTE (2% versus 0.16%; P=0.002) and major bleeding (3.7% versus 0.6%; P<0.001). Bridging with heparin increased the rate of major bleeding in cancer patients (5% versus 1%; P=0.03) without impacting the VTE rate (0.7% versus 1.4%, P=0.50). CONCLUSIONS: Cancer patients anticoagulated for VTE experience higher rates of periprocedural VTE and major bleeding. Periprocedural anticoagulation for these patients requires particular attention to reduce these complications.

Predictors of major bleeding in peri-procedural anticoagulation management.

BACKGROUND: Appropriate periprocedural management for chronically anticoagulated patients requires assessment of patient-specific thrombosis and bleeding risks. However, predictors of post-procedure bleeding are unknown. OBJECTIVES: To determine the 3-month cumulative incidence and independent predictors of peri-procedural bleeding in chronically anticoagulated patients requiring temporary warfarin interruption for an invasive procedure. METHODS: In a protocol driven, cohort study design, all patients referred to the Mayo Clinic Thrombophilia Center for peri-procedural anticoagulation management (1997-2007; n = 2182), were followed forward in time to determine the 3-month cumulative incidence of peri-procedural bleeding (Kaplan-Meier product limit) and potential predictors of bleeding (Cox proportional hazards). Decisions to 'bridge' with low-molecular-weight heparin were based on estimated thromboembolism and bleeding risk. RESULTS: Indications for chronic anticoagulation included venous thromboembolism (38%), atrial fibrillation (30%) and mechanical heart valves (27%). Of these, 1496 (69%) patients received bridging therapy. The 3-month cumulative incidence rates of major and overall bleeding were 2.1% and 5.1%, respectively. Major bleeding occurred more frequently in patients receiving bridging therapy (3% vs. 1%; P = 0.017). Independent predictors (hazard ratio; 95% confidence interval) of major bleeding included mitral mechanical heart valve (2.2; 1.1-4.3), active cancer (1.8; 1.0-3.1), prior bleeding history (2.6; 1.5-4.5) and re-initiation of heparin therapy within 24 h after the procedure (1.9; 1.1-3.4). CONCLUSION: Factors predisposing to peri-procedural bleeding are primarily patient-specific. Premature heparin re-initiation is an avoidable provider-specific variable to consider.

Predicting superficial venous incompetence with strain gauge plethysmography.

BACKGROUND: With currently available effective interventional methods to treat superficial venous insufficiency, it becomes particularly important to have a simple and reliable method to evaluate the location and severity of venous reflux. To date, there are few studies that evaluated plethysmography with and without tourniquet application to differentiate superficial from deep venous incompetence. OBJECTIVES: To determine if strain gauge plethysmography (SGP) with and without tourniquet application can be used to distinguish between the superficial and deep venous components of venous incompetence. METHODS: We conducted a prospective study using SGP with and without tourniquet application and duplex ultrasound (duplex US) to assess the severity and location of venous incompetence in 62 patients (85 limbs, 42 women, with an age range of 32-81 years) referred to our vascular laboratory for haemodynamic evaluation. Based on duplex US results, patients were diagnosed with superficial (SVI), deep and superficial (mixed) and deep vein incompetence (DVI). RESULTS: Mixed incompetence was the most common type. Twenty-three out of 33 limbs in the SVI group normalized their refill rate (RR) with tourniquet application (69.6%). Normalization of the RR with tourniquet application was less common in the mixed (n: 17 out of 40, 42.5%) and DVI (n: 2 out of 6, 33.3%) groups. CONCLUSION: SGP with tourniquet application is a simple and fast technique that can identify patients with SVI, based on RR improvement, who probably would benefit more from ablation procedures. Further studies evaluating impact of SGP with tourniquet test results on clinical outcome of SVI invasive treatment are warranted.

Iliac vein thrombosis: feasibility assessment of randomized controlled trials of endovascular pharmacomechanical thrombolysis.

BACKGROUND: Optimal treatment for iliac vein thrombosis has not been established by randomized clinical trials largely owing to difficulty in patient recruitment. To assess the feasibility of a prospective randomized trial of thrombolysis and stenting, we determined the incidence of iliac vein thrombosis and randomization eligibility based on criteria for two ongoing trials. METHODS: All patients with incident leg deep vein thrombosis during the calendar year 2005 seen at the Mayo Clinic were identified to determine the frequency of iliac vein involvement and the number undergoing endovascular therapies. Each patient was assessed for eligibility for potential randomization into a theoretic trial of thrombolytic therapy. RESULTS: Ninety-five (of 394) patients had iliac vein involvement. Of these, only nine patients would have been suitable for randomization. Of the remaining 86 patients, prolonged symptom duration (n = 28), active cancer (n = 24) and advanced age (n = 19) were the most common exclusion criteria. Of 31 patients who had intervention, 75% had at least one contraindication for randomization. CONCLUSIONS: Despite a philosophy of aggressive treatment for iliac vein thrombosis at this institution, the number of cases that could potentially be randomized into a clinical trial is relatively small. Trial design may require either multicenter cooperation or exclusion criteria revision for adequate recruitment.

Intermittent pneumatic compression in stable claudicants: effect on hemostasis and endothelial function.

AIM: Intermittent pneumatic compression (IPC) increases systemic fibrinolytic activity but may also injure endothelial cells and thereby induce coagulation. The safety and utility of IPC in patients with peripheral arterial disease (PAD) therefore remains uncertain. The aim of this study was to determine whether IPC is associated with coagulation activation and endothelial cell damage, platelet factor 4 (PF4), thrombin-antithrombin complex (TAT), total nitrate and nitrite level and von Willebrand factor (VWF) concentration. METHODS: PF4, TAT, total nitrate, nitrite level and VWF were analyzed before and after first, 5th, 15th session (1 hour/day) of IPC and then 3 weeks after completion of therapy in 25 claudicants and compared to 11 healthy volunteers of similar age and sex. RESULTS: PF4, a measure of platelet activation/secretion, was significantly higher in claudicants (55+/-50 IU/mL) compared to healthy controls (22+/-14 IU/mL) (P<0.05). In PAD patients PF4 has decreased steadily and significantly throughout the time of compressive therapy (to 33+/-42 IU/mL) and further more at the end of the follow-up period (23+/-26 IU/mL). TAT concentration was low in PAD patients but further decreased during IPC therapy. There was a tendency of nitrite and nitrate concentration to increase during the course of IPC therapy, but in PAD patients it did not reached statistical significance (P=0.2), while in healthy controls this increase was significant (up to 79+/-14 mmol/L, P<0.05) and persisted 3 weeks after completion of IPC (up to 82+/-7 mmol/L, P<0.05). VWF antigen concentration remained stable in claudicants during IPC therapy and 3 weeks later but significantly decreased during IPC therapy (after fifth and fifteenth IPC session, P=0.04) and stayed decreased 3 weeks after treatment termination in control group. Pain-free walking distance (PWD) had increased continuously during treatment period from 55+/-23 to 63+/-32 meters after fifth IPC treatment, to 81+/-43 (P<0.05) after the last session of therapy, and slightly decreased to 77+/-28 meters 3 weeks after completion of IPC. CONCLUSIONS: IPC is safe for PAD patients, does not activate coagulation, but decreases platelet activation and improves endothelial health; this coincides with significant prolongation of walking distance.

Thrombophilia differences in cerebral venous sinus and lower extremity deep venous thrombosis.

OBJECTIVE: To characterize differences in the prevalence of thrombophilic variables in a large cohort of patients with cerebral venous sinus thrombosis (CVST) and lower extremity deep vein thrombosis (DVT). METHODS: An inception cohort of individuals was identified with first lifetime incident CVST between 1995 and 2005 for whom comprehensive thrombophilia testing was available. To test the hypothesis that thrombophilia prevalence differs with respect to thrombus location, test results were compared to a randomly selected group of patients with lower extremity DVT with comprehensive thrombophilia testing. RESULTS: During this time period, 163 patients with CVST were identified who underwent comprehensive thrombophilia testing. Thrombophilia results were abnormal in 29% including anticardiolipin antibodies (17%), heterozygous factor V Leiden (10%), and heterozygous prothrombin G20210A mutation (n = 14/122; 11%). The prothrombin mutation was more than twice as common in patients with CVST (p = 0.04). Activated protein C resistance, factor V Leiden, and protein C deficiency were more common in patients with DVT (p < 0.05 for each comparison). The anticardiolipin antibodies in patients with CVST were primarily low titer IgM isotype. CONCLUSION: The prevalence of selected thrombophilia factors differs comparing patients with cerebral venous sinus thrombosis and deep vein thrombosis. These differences may offer insights into mechanisms governing the geographic distribution of venous thrombosis.

Prevalence of lower extremity venous disease in inflammatory bowel disease.

AIM: Inflammatory bowel disease (IBD) has long been considered a risk factor for venous thromboembolism (VTE). Whereas most patients have persistent venous valvular dysfunction following lower extremity deep venous thrombosis (DVT), we hypothesized that patients with IBD would have an increased prevalence of valvular incompetence and changes of chronic DVT (reduced venous caliber with thickened walls) relative to patients with irritable bowel syndrome (IBS) or normal volunteers. METHODS: Subjects with confirmed IBD, clinical features of IBS or normal volunteers underwent complete, prospective duplex ultrasound assessment of their lower extremity venous vascular system. The sonographer performing the venous study was blinded to the clinical diagnosis of the patients. Valvular incompetence was graded as mild, moderate or severe based on accepted criteria. RESULTS: Eighty patients with IBD (ulcerative colitis, UC: 66; Crohn's disease: 14), 80 patients with IBS, and 80 healthy volunteers agreed to participate. One patient with UC was found to have non-occlusive chronic DVT within the left superficial femoral vein. Mild and moderate valvular incompetence was evenly distributed between the 3 groups. No patients met criteria for either acute DVT or severe venous incompetence. CONCLUSION: In patients with IBD, neither valvular incompetence nor chronic venous obstruction are over-represented compared to patients with IBS or normal volunteers. In this prospective assessment of venous physiology by duplex ultrasound, we were not able to confirm prior reports that IBD is a major risk factor for VTE.

Cerebral venous sinus thrombosis: Incidence of venous thrombosis recurrence and survival.

OBJECTIVE: To determine whether treatments guidelines for lower extremity venous thrombosis (DVT) could be applied to patients with cerebral venous sinus thrombosis (CVST), the rates of recurrent venous thrombosis and survival for these two diseases were compared. METHODS: The authors studied all patients diagnosed with CVST at the Mayo Clinic between 1978 and 2001. Survival and recurrent venous thrombosis rates (cerebral or noncerebral) were compared with those from patients with DVT. Survival rates were also compared with white US residents. RESULTS: One hundred fifty-four patients (age 40 +/- 19 years) were included (58% women). Warfarin, prescribed in 50% of patients, was continued for an average of 9 months. During a mean of follow up of 36 +/- 47 months (464 patient-years), 20 patients experienced 23 recurrent venous thrombi for an event rate of 5.0/100 patient-years. This recurrence rate was similar to patients with lower extremity DVT (3.8/100 patient-years). Mortality rates were lower for CVST (2.8/100 patient-years) compared with DVT (6.2/100 patient-years; p = 0.001) patients but higher than expected for white US residents (p = 0.001). Increasing age and active malignancy were the only predictors of poor survival. Neither recurrent thrombosis nor survival was influenced by warfarin therapy. CONCLUSIONS: The likelihood of recurrent venous thrombosis is similar after cerebral venous sinus thrombosis (CVST) and lower extremity deep venous thrombosis (DVT). Compared with DVT, survival rates are higher following CVST but are adversely influenced by malignancy and older age.

Atrial fibrillation and thrombosis: immunohistochemical differences between in situ and embolized thrombi.

BACKGROUND/OBJECTIVE: Thromboembolism secondary to atrial fibrillation accounts for approximately one-fourth of all strokes. Although considerable resources have been targeted to pharmacologic prophylaxis, neither the cellular nor the biochemical composition of atrial thrombi is known. Quantitative immunohistochemistry was undertaken to define the composition of atrial thrombi and to explore morphological differences between atrial appendage thrombi and those that embolize. PATIENTS/METHODS: Serial sections of thrombi obtained during valve replacement surgery or embolectomy from 22 patients with atrial fibrillation were stained with antibodies against fibrin, integrin beta3, or tissue factor and analyzed with NIH-image. RESULTS: Thrombi showed distinct regions staining for either fibrin or platelets and on average, the fibrin-rich regions predominated (P < 0.0001). The platelet content of embolized thrombi was nearly twice that of atrial thrombi (P = 0.02). Non-staining amorphous material comprised nearly half of atrial thrombi in situ, but was rare in embolized thrombi (P < 0.001). Tissue factor colocalized to areas rich in platelets and granulocytes. CONCLUSIONS: The abundance of fibrin relative to platelets underscores the enhanced efficacy of warfarin prophylaxis in clinical trials. The finding of tissue factor localized to platelet-leukocyte clusters suggests its blood-borne origin. Compositional differences between in situ and embolized thrombi suggest directions for investigating propensity for embolization.

Coagulation in diabetic and non-diabetic claudicants.

BACKGROUND: In order to compare hemostasis in diabetic and non-diabetic claudicants we evaluated endothelial (von Willebrand factor, vWF), rheologic (fibrinogen, hematocrit), coagulation system (thrombin-antithrombin complex, TAT) and platelet (platelet factor 4, PF4, aggregation on thrombin, collagen and ADP stimulation) parameters in both groups and healthy controls. METHODS: Twenty-five diabetic, 34 non-diabetic patients with claudication and 26 healthy individuals were enrolled into the study. RESULTS: The severity of lower limbs ischemia was similar in two groups of claudicants but coronary heart disease and cerebral ischemia were significantly more common in diabetic than in non-diabetic claudicants. vWF level was significantly higher in diabetic than non-diabetic claudicants and healthy controls (184+/-43%, 147+/-43%, and 103+/-42%, respectively). Fibrinogen was significantly higher in diabetic and non-diabetic claudicants compared to controls (4.2+/-1.7, and 3.9+/-1.1, versus 2.9+/-0.5 g/l) and TAT plasma concentration was much higher in diabetic compare to non-diabetic patients and controls (9.8+/-4.4, 1.7+/-1.1, and 1.3+/-0.6 microg, respectively). PF4 concentration was significantly higher in non-diabetic patients with PAOD (34+/-29 UI/ml) when compare to healthy controls (14+/-9 UI/ml), but diabetic PAOD patients with the disease showed lower PF4 concentration (26+/-30 UI/ml). Platelet aggregation with all used activators was similar in all groups likewise hematocrit values, and platelet count. CONCLUSIONS: Complicated DM is linked with significant endothelial perturbation when compared with healthy, but also with PAOD individuals; rheologic parameters are not different from those found in PAOD patients; coagulation system activation but not platelet hyperactivity is associated with DM complicated by PAOD when compared to both control groups.

Clinical spectrum of Raynaud's phenomenon in patients referred to vascular clinic.

Difficulties to establish general characteristics of patients with Raynaud's phenomenon, especially frequency, rates and predisposing factors of the evolution of primary to secondary cases probably originate from substantial variation of evaluated cohorts. We conducted a prospective study using standardised diagnostic procedures in order to look for the specificity of patients referred to the vascular centre; moreover, we assayed anticardiolipin antibodies in these patients using double ELISA and compared its frequency to sex and age matched a control group of 50 healthy individuals. 124 patients (20 men), mean age at onset 35.5 yr, range 9-69 yr, had confirmed diagnosis of Raynaud's phenomenon. Ninety nine patients were found to have secondary phenomenon, 72% of them had trophic changes of fingers and/or toes. Anticardiolipin antibodies assay was positive in seven patients and four healthy donors. Vascular diseases constituted about 20%, and connective tissue diseases 50% of secondary cases, but SLE (17 cases) not a scleroderma (11 cases) was the most frequent clinical entity in the latter group. There were only two patients with Buerger's disease and one with atherosclerosis as an underlying disease for vasospastic disorder. We concluded in the vascular medicine centre that there were a lot of patients with ischemic necrosis or other type of trophic changes, and very little primary, benign Raynaud's disease cases; surprisingly, peripheral arterial occlusive disease was very seldom responsible for vasospastic episodes. Primary or secondary antiphospholipid syndrome is not associated with Raynaud's phenomenon.

Sustained classic clinical spectrum of thromboangiitis obliterans (Buerger's disease).

Thromboangiitis obliterans (TAO) has been reported to become less common in general population but more common in women, and in elderly patients. The authors looked at the clinical characteristics of TAO in Poland where there was no significant decrease of smoking and the extent of aging of the general population is less profound. They retrospectively reviewed the records of 377 patients with the diagnosis of TAO hospitalized in their institution from 1970 to 1995. If young smoking males demonstrated distal-extremity ischemia with no bruits audible over major arteries, upper limbs involvement, or superficial thrombophlebitis, the diagnosis of TAO was considered certain. When at least one of those criteria was missed, and in men older than 35 years, but in all females, typical arteriographic findings were required for the diagnosis of TAO. Connective-tissue disease, hyperlipidemia, diabetes, and hypercoagulable state were excluded. Three hundred forty-two men (91%), and 35 (9%) women had a mean age of 29.5 years at the onset of the disease (the oldest patient was 50 years old). The prevalence of TAO in southwest Poland is 8.1/100,000 and the incidence of the disease steadily declines; there was no increase of TAO in women. Three hundred thirty-seven (89%) experienced rest pain, 321 (85%) had ischemic necrosis, and 233 (62%) thrombophlebitis at some (continued on next page) time in the course of the disease. Raynaud's phenomenon occurred in only 39 patients (10%). Those patients who had quit smoking had a 50% decrease of the disease recurrences compared to their smoking period. Because the cause of declining incidence of TAO is obscure, the authors critically evaluated previously used explanations of this phenomenon. They did not confirm the observation of a change in the TAO clinical spectrum: occurrence in women did not increase, the aging of the TAO population was not observed. In Poland TAO is still a disease affecting the peripheral circulation of young smoking males with recurrent episodes of superficial thrombophlebitis and common involvement of the upper extremities; Raynaud's phenomenon is rather infrequent. Smoking cessation ameliorates the course of the disease but does not invariably stop further exacerbations.

Individual propensity for arterial thrombosis.

Arterial thrombophilia independent of vascular pathology has not been previously defined either experimentally or epidemiologically. To address the existence of an individual propensity to arterial thrombosis, we exploited a previously developed procedure entailing traumatic (crush) injury of paired porcine carotid arteries for generating platelet-rich thrombi. Porcine carotid arteries were injured bilaterally by serial hemostat crushes. Thrombus generation was monitored by local accumulation of autologous 111In-labeled platelets and Doppler blood flow. Within this cohort of animals of similar age and size, the lowest to the highest responders in thrombus mass spanned a 7-fold range, showing no correlation with shear, platelet or leukocyte count, or plasma concentrations of fibrinogen or von Willebrand factor. However, there was strong intra-individual correlation (r2=0.80; P<0.001) of thrombus deposition between carotid artery pairs. The wide variation in thrombotic response to a standardized stimulus, not accounted for by shear stress or typical hematological variables, appears to be an intrinsic propensity of the individual. The experimental system for thrombus generation is sufficiently quantitative for assessment of variables determining this propensity.

Dobutamine effect on ankle-brachial pressure index in patients with peripheral arterial occlusive disease. New noninvasive test for evaluation of peripheral circulation?

BACKGROUND: This study was designed to evaluate the effect of short-term administration of graded dose of dobutamine on the circulation of the lower limbs in the patients with symptomatic peripheral arterial occlusive disease. METHODS: An ankle-brachial pressure index (ABI) was determined at the time of dobutamine stress echocardiography by measuring systolic pressure over the brachial artery and right dorsalis pedis artery using continuous-wave Doppler instrument. Setting. The study was conducted on all patients who had dobutamine stress echocardiography ordered by their referring physicians and performed in the Echocardiography Laboratory of the Mayo Clinic. Patients. All patients scheduled for dobutamine stress echocardiography were the subject of this study unless they had rigid vessels defined as ABI > 1.5, were on beta-blockers or did not agree to participate in the study. 20 patients, mean age 67 +/- 9 years (9 men and 11 women) without peripheral occlusive arterial disease and resting ABI > or = 1.0 (group A), and 18 patients, mean age 71 +/- 10 years (11 men and 7 women) with the evidence of peripheral occlusive arterial disease and ABI < 1.0 were examined. Measures. ABI was measured just prior to starting the dobutamine infusion, and then at the third minute of each increment in dobutamine dosage. RESULTS: In control group patients ABI rises at 5-10 micrograms/kg/min of dobutamine infusion and at higher doses (20-50 micrograms/kg/min) drops back to the baseline values. In the patients with peripheral arterial occlusive disease low doses of dobutamine do not increase ABI, but higher doses cause decrease of pressure index from 0.6 to 0.3. There was no incidence of ischemic pain or any other kind of discomfort in the lower extremities. CONCLUSIONS: Low doses of dobutamine have no decremental effect on peripheral circulation. High doses of dobutamine cause a profound decrease of blood pressure in the lower limbs of patients with peripheral occlusive arterial disease, and the extent of decrease was proportional to the degree of ischemia. Peripheral blood pressure changes registered in the study over dorsalis pedis artery at the time of dobutamine infusion resemble those that occurred at the time of exercise-walking test. ABI measurement at the time of dobutamine echocardiography might be a useful test for the evaluation of peripheral circulation. Further studies are necessary for the assessment of a clinical usefulness of dobutamine-ankle-brachial test.

Buerger's disease in two brothers: iliac artery occlusion by thromboangiitis obliterans--case reports.

Several characteristics of thromboangiitis obliterans are unique and confirm the existence of the disease as a distinct pathological entity. Its predilection for young smoking males, peripheral type of vascular involvement, recurrences of superficial thrombophlebites, and typical histolopathology form the principals of the disease although the etiology remains unknown. The authors report the unusual finding of Buerger's disease occurring in two brothers, one of whom had occlusion of the left external iliac and femoral arteries. All other clinical characteristics of these two cases were typical for thromboangiitis obliterans. Presentation of some peculiarities of the disease, particularly the lack of familial association, may help to unravel the pathogenesis of thromboangiitis obliterans.

Reversibility of platelet thrombosis in vivo. Quantitative analysis in porcine carotid arteries.

Reversibility in vivo of acute platelet thrombosis in response to specific anticoagulants is analyzed with thrombi that develop in segments (1 cm) of porcine carotid arteries externally crushed with a hemostat. Most thrombi fill the lumens of the injured segments (ca. 1 cm x 3 mm, 1 x w) within 30 min and comprise masses of platelets interpenetrated with neutrophil-lined seepage channels of blood. Continuous quantitative assay of thrombus mass is provided by a gamma detector placed over the injured segments to collect counts from 111In-labeled platelets. Thrombi established 30 min after injury, otherwise stable for 6 h, clear during 30-60 min of continuous infusion of either hirudin, tick anticoagulant or activated porcine protein C, or intermittent activation of endogenous protein C with a latent thrombin reagent. Anticoagulant dose-dependence of thrombus clearance is established for hirudin between 0.01 and 1.0 mg/kg/min. Thrombi become progressively refractory to hirudin between 0.5 and 6 h after injury. Neither heparin no low-molecular-weight heparin in full (clinical) anticoagulant doses yield significant dethrombosis. It is concluded that, within time limits, controlled thrombin generation in platelet thrombi maintains platelet cohesion without catalyzing irreversible platelet aggregation or clotting of fibrinogen.

Antithrombotic action of endogenous porcine protein C activated with a latent porcine thrombin preparation.

Endogenously activated protein C is evaluated for antithrombotic activity in porcine carotid arteries subjected to mechanical trauma. Protein C is activated by intravenous administration of guanidinobenzoyl-thrombin, which binds to thrombomodulin and there deacylates to yield thrombin. The bound, transiently active thrombin yields a peak of anticoagulant activity between 5 and 10 min after infusion of the latent thrombin. Inhibition of thrombin binding in vivo by co-infusing and active-site-blocked thrombin preparation elicits acute and lethal systemic thrombosis. Nearly occlusive platelet thrombosis, which occurs within 30 min of crushing 1 cm segments of carotid arteries with a standard hemostat, is blocked by endogenous protein C activation initiated 2 min before the crush injury. It is concluded that activated protein C blocks thrombosis is deeply injured musculo-elastic arteries, and that activation of latent thrombin bound to thrombomodulin in vivo is a practical means for delivery of pharmacologically effective concentrations of activated protein C.