Lepirudin is a safe and effective anticoagulant for patients with heparin-associated antiplatelet antibodies.

OBJECTIVE: The purpose of this study was to determine whether lepirudin, a direct thrombin inhibitor, is a safe and effective anticoagulant for patients with heparin-associated antiplatelet antibodies (HAAbs). METHODS: The charts of HAAb-positive patients who received lepirudin were reviewed. Lepirudin use was analyzed for indication, duration, and effectiveness of anticoagulation, and for adverse events. HAAb presence was determined by platelet aggregation. RESULTS: Eighteen HAAb-positive patients received lepirudin: 9 had previous documentation of HAAb, 6 had thrombocytopenia while receiving heparin; and 3 had HAAb after a thrombotic event. The indications for lepirudin anticoagulation included thromboembolism prophylaxis (5), arterial thromboses (5), pulmonary embolus (3) or deep venous thrombosis (1), and one each for atrial fibrillation, myocardial infarction, artificial heart valves, and hemodialysis access. The average duration of therapy was 4.04 days. Fifteen patients achieved adequate anticoagulation (activated partial thromboplastin time [aPTT] ratio > 2.0) with lepirudin. Seven patients had aPTTs that were sometimes supratherapeutic (aPTT > 100 seconds) but did not bleed. In all patients who had heparin-induced thrombocytopenia, platelet counts were normalized while they received lepirudin. There were two complications: one patient fell and had a calf hematoma (aPTT ratio 3.24), and one patient who received lepirudin during nine separate hospitalizations had epistaxis (aPTT ratio 2.86) during her ninth hospitalization. Another patient received lepirudin during two hospitalizations without an adverse event. CONCLUSION: Lepirudin is a safe and effective anticoagulant for patients with HAAbs. The platelet counts of all patients with heparin-induced thrombocytopenia were normalized while they received lepirudin. Careful monitoring of the aPTT and avoidance of trauma while patients are receiving lepirudin are recommended.

Use of enoxaparin in patients with heparin-induced thrombocytopenia syndrome.

PURPOSE: To determine whether low molecular weight heparin (LMWH) can be an alternative to unfractionated heparin (UH) for patients with heparin-induced thrombocytopenia syndrome (HIT). METHODS: The diagnosis of HIT was established in 126 patients by platelet aggregometry with UH (1 U/ml). These plasma samples were also tested for the ability to aggregate platelets in the presence of the LMWH enoxaparin (1 U/ml). Two patients with the HIT syndrome, after negative platelet aggregometry testing with enoxaparin, were anticoagulated with enoxaparin. RESULTS: Fifteen plasma samples that tested negative to UH also tested negative to enoxaparin. Forty-three of 126 (34%) UH-positive plasma samples aggregated platelets in the presence of enoxaparin. Twenty-two of 102 (22%) plasma samples with limited positive aggregation responses (minimal or no change in optical density) aggregated platelets in the presence of enoxaparin. However, 21 of 24 (88%) strongly positive plasma samples (30% to 60% change in optical density at 3 to 27 minutes) also aggregated platelets in the presence of enoxaparin. Two patients with HIT who received enoxaparin after aggregation testing demonstrated no cross-reactivity to enoxaparin achieved adequate anticoagulation and did not develop HIT. CONCLUSIONS: Thirty-four percent of plasma samples from patients with HIT (88% of those strongly positive) aggregated platelets in the presence of enoxaparin. Patients with HIT may safely receive enoxaparin if their plasma does not aggregate platelets in the presence of enoxaparin.

The effects of endothelin-1 on collagen type I and type III synthesis in cultured porcine coronary artery vascular smooth muscle cells.

Restenosis is the single most important factor limiting a favorable long-term outcome following mechanical revascularization. The vascular endothelium, through the release of key regulatory compounds, may regulate vascular structure by exerting fundamental control over collagen synthesis following injury to the vessel wall. We tested the hypothesis that endothelin (ET-1), an endothelium-derived peptide previously shown to be increased in pathological states, differentially stimulates porcine coronary vascular smooth muscle cell collagen types I and III synthesis. Monocultures of porcine coronary vascular smooth muscle were exposed to varying concentrations of endothelin over a 24-96-h time period. The medium was assayed for soluble collagen types I and III using a sensitive and specific ELISA method. Experiments were also done with the ET-1 antagonists PD 145065 and BQ123. Cell counts and viability were serially monitored. Experiments were also conducted with angiotensin II (A-II). A-II and ET-1 stimulated cell proliferation. ET-1 maximally stimulated collagen type I synthesis at 48 h at an optimal concentration of 10(-8) M, with no significant stimulation of collagen type III synthesis. The ETA specific antagonist BQ123 significantly inhibited the stimulatory effects of ET-1. A-II also stimulated collagen type I synthesis above basal levels, but was less efficacious than endothelin (95 +/- 5%, A-II, v 189 +/- 14% ET-1). In contrast to ET-1, A-II stimulated collagen type III synthesis (31 +/- 6% above basal, compared to -4 +/- 5% for ET-1). Results are also reported using smooth muscle cells from porcine aorta. The data demonstrate that ET-1 and A-II stimulate collagen synthesis by coronary artery vascular smooth muscle, and that they exert a differential effect over the two types of collagen that are present in the intima following balloon injury. Thus, the over expression of key regulatory compounds by endothelium following balloon injury could enhance collagen deposition and, consequently, play an integral role in intimal hyperplasia and restenosis.

Spontaneous common carotid artery dissection.

A case of a symptomatic spontaneous common carotid artery dissection that occurred several months after an ipsilateral carotid endarterectomy is presented. The case was successfully managed with resection of the dissected common carotid artery and placement of an interposition saphenous vein graft. Examination of the specimen demonstrated cystic medial degeneration. Postoperative duplex scans of the carotid artery and graft have been normal. The data obtained from this case and a review of the seven previously reported cases suggest that surgical management of symptomatic spontaneous common carotid artery dissections can be accomplished safely. Surgical management of these dissections is recommended for patients with symptoms and for those without symptoms who have aneurysmal changes in the dissected segment.

Tissue plasminogen activator treatment of digital thrombosis in severe Raynaud's phenomenon--a case report.

A thirty-one-year-old woman with long-standing mixed connective tissue disease and severe obliterative vasculopathy of the digits developed digital thrombosis of the first three digits of the left hand after using an electric blow dryer. The digits remained cool, cyanotic, and painful for thirty-six hours before medical evaluation. She was given 100 mg recombinant tissue plasminogen activator (TPA) intravenously. Within one hour the blood flow to the digits returned, accompanied by severe intermittent vasospasm of the digits. The thumb did not necrose; however, the second and third digits required amputation. No improvement was noted in the patient's baseline Raynaud's phenomenon or digital pressures of the uninvolved digits after TPA treatment. This case documents the usefulness of TPA for digital thrombosis in the setting of vasculopathy of connective tissue disease. However, it does not support the utility of a single dose of TPA for severe Raynaud's phenomenon and recurrent digital ischemia in patients with connective tissue disease.

Color-flow duplex scanning for the surveillance and diagnosis of acute deep venous thrombosis.

Compared with conventional duplex imaging, color-flow scanning facilitates the identification of veins (especially below the knee), decreases the need to assess Doppler flow patterns and venous compressibility, and allows veins to be surveyed longitudinally. These advantages translate into a less demanding and time-consuming examination. This study was designed to determine the accuracy of color-flow scanning for detecting acute deep venous thrombosis in patients in whom the diagnosis is clinically suspected and in asymptomatic patients at high risk for developing postoperative deep venous thrombosis. The diagnostic group included 77 limbs of 75 patients, and the surveillance group included 190 limbs of 99 patients undergoing total hip or knee replacement. All patients were prospectively examined with color-flow scanning and phlebography. In the diagnostic group, the incidence of thrombi in below-knee veins (47%) was approximately equal to that in above-knee veins (43%); but in the surveillance group, the incidence of thrombi in below-knee veins (41%) far exceeded that in veins above the-knee (3%). Nonocclusive clots and clots isolated to a single venous segment were more common in the surveillance group. In symptomatic patients, color-flow scanning was 100% sensitive and 98% specific above the knee and 94% sensitive and 75% specific below the knee. In the surveillance group, color-flow scanning was significantly (p less than 0.001) less sensitive (55%) for detecting thrombi, 93% of which were confined to the tibioperoneal veins. Negative predictive values were 100% and 88% for the diagnostic and surveillance limbs, respectively. Positive predictive values were 80% for the diagnostic limbs and 89% for the surveillance limbs. Color-flow scanning effectively excludes above-knee deep venous thrombosis in symptomatic patients and asymptomatic high-risk patients and predicts the presence of above-knee thrombi in patients in the diagnostic group with reasonable accuracy (97%). We conclude that color-flow scanning is as accurate as conventional duplex imaging and, because of its advantages, is the noninvasive method of choice for evaluating patients with suspected deep venous thrombosis. Its role in the surveillance of patients at high risk remains to be determined and awaits further clinical evaluation.

Does color-flow imaging improve the accuracy of duplex carotid evaluation?

To determine whether color-flow imaging enhances the accuracy of noninvasive carotid evaluation, the results of carotid duplex examinations from two laboratories, one with color-flow and the other with standard duplex imaging were compared. The techniques used by both laboratories were identical. All studies were interpreted by one of the authors, using the same criteria. From October 1988 through December 1989, 307 internal carotid arteries were evaluated with both color-flow imaging and standard angiography; and 206 underwent routine duplex scanning and angiography. Perfect agreement between test and angiographic results was significantly better with color-flow (86.6%) than with conventional duplex scanning (79.6%), p = 0.034 (t test for independent samples). Significantly fewer vessels were over classified by one category with color-flow (8.5%) than with routine duplex scanning (16.5%), p = 0.006. However, no difference was found in the number under-classified by one category (4.5% vs 3.4%), p = 0.5. Although these data support the accuracy of both modalities, there appears to be a trend toward improved results with the newer method. We attribute this to more precise placement of the pulsed Doppler sample volume afforded by the color-flow image.

Initial experience with color-flow duplex scanning of infrainguinal bypass grafts.

Seventy-eight infrainguinal grafts were evaluated by means of color-flow duplex imaging to demonstrate its utility in the routine surveillance of leg grafts as well as in the evaluation of grafts in which a problem is already suspected. Stenoses were identified in 15 (20%) of 76 grafts evaluated for screening purposes. Seven of these had confirmatory arteriograms, and five were revised. The remaining eight grafts with suspected stenoses were followed without angiography, and four (50%) subsequently failed. Only two (3.3%) of 61 grafts with normal scan outcomes have thrombosed. Fistulas were identified in 12 (37%) of 32 in situ grafts evaluated. Nine grafts with previously suspected problems based on decreased ankle-brachial indexes were scanned, and an explanation was found, confirmed by angiogram, and corrected in six. Detection of unsuspected stenoses in five grafts requiring revision and four grafts that later thrombosed without revision, as well as identification of fistulas in 37% of in situ grafts, confirms the importance of color-flow imaging as a screening tool.

Contralateral internal carotid artery stenosis or occlusion: pitfall of correct ipsilateral classification--a study performed with color-flow imaging.

The records of 183 patients who had undergone color-flow imaging of the extracranial carotid arteries and subsequent bilateral cerebral arteriography were reviewed to determine whether contralateral carotid arterial disease adversely affects the accuracy of duplex scanning by increasing the velocity of flow in the ipsilateral artery. In 83 arteries the contralateral internal carotid artery had a diameter reduction greater than or equal to 80%; in the remaining 283, the contralateral artery was less severely diseased. Noninvasive findings correlated less well with arteriography in the group with contralateral disease (k = 0.69 +/- 0.06) than in the group with less severe contralateral stenosis (k = 0.78 +/- 0.03), and the incidence of false-positive errors was significantly (p = 0.02) higher (18% vs 7%). For all categories of ipsilateral stenosis, the mean peak systolic and end-diastolic velocities were elevated in the group with severe contralateral disease. This effect was most evident in the 50% to 79% diameter reduction category, especially in reference to the end-diastolic velocity (p = 0.2). However, the data correlating velocity with diameter reduction were widely scattered, indicating that the effect of contralateral disease is inconsistent. We conclude that severe disease of the contralateral carotid artery can lead to overreading ipsilateral disease and that velocity determinations should be interpreted cautiously under such circumstances.

Neovascularization of surface demineralized dentin.

Uneventful healing of the wound site created by periodontal reconstructive surgery is crucial for the long term survival of the dentition. Wound healing has been shown to be initiated and mediated by matrix components and polypeptide growth factors. Neovascularization (or angiogenesis) is one of the most important events in the healing process of a wound site. Any increase in the degree and/or rate of neovascularization could result in more rapid or complete healing. Previously, we have shown that basic fibroblast growth factor (bFGF) selectively enhances periodontal ligament cell migration and proliferation. In addition, we have shown that FGF stimulates human umbilical vein endothelial cell migration and proliferation. In this study we examined whether human umbilical vein endothelial cells could be influenced to form capillary-like structures in a type I collagen stroma and on dentin surfaces in response to fibroblast growth factor (FGF). We observed tubule-like structures formed from a monolayer of endothelial cells within a type I collagen sponge in response to a gradient of FGF. Furthermore, we observed tubule-like structures formed from self-association of individual endothelial cells on partially demineralized dentin surfaces in response to FGF. Proliferation of human endothelial cells on dentin was dose dependent and maximally stimulated at a concentration of 10 ng/ml FGF. These data indicate that FGF can induce endothelial cell migration, proliferation and tubule formation on dentin.

Repopulation of dentin surfaces by periodontal ligament cells and endothelial cells. Effect of basic fibroblast growth factor.

The regeneration of connective tissue attachment is a major goal of clinical periodontics. Recent investigations on biochemically mediated periodontal regeneration have attempted to define the various biological response modifiers which may provide a mechanism for periodontal regeneration. Fibronectin and endothelial cell growth factor have been shown to selectively enhance periodontal ligament (PDL) cell adhesion, migration, and proliferation. In addition, dentin preconditioned with tetracycline HCl (TTC) or citric acid (CA) supports PDL cell adhesion, presumably by exposing collagen fibers. We have now extended these studies to include basic fibroblast growth factor (b-FGF) as a potential meditor of periodontal regeneration. Using AFSCM (assays for specific cell migration), b-FGF in concentrations as low as 10 ng per dentin block significantly stimulated PDL cell chemotaxis, while the antibody against b-FGF inhibited both the chemotactic and proliferative characteristics of the mitogen. We also found that 5 ng and above of b-FGF per dentin block significantly stimulated human endothelial cell migration and proliferation. Using 125I-b-FGF, we demonstrated that the factor binds to native dentin. This binding was increased when the dentin blocks were preconditioned by TTC or CA and reduced when the dentin was subsequently treated with collagenase. 125I-b-FGF also bound with moderate affinity to a type I collagen affinity column whereas the binding to a hydroxylapatite affinity column was negligible. The combination of FN and b-FGF was a marginally more potent chemo-attractant than b-FGF alone for PDL cells.(ABSTRACT TRUNCATED AT 250 WORDS)