Assessing Mailuoning injection in wound healing and thrombophlebitis management: A rat model study.

Thrombophlebitis is the inflammatory condition characterized by obstruction of one or more vessels, commonly in the legs, due to the formation of blood clots. It has been reported that traditional Chinese medicine, including Mailuoning injection, is advantageous for treating inflammatory and blood disorders. This research assessed the therapeutic efficacy of Mailuoning injection in the treatment of thrombophlebitis in rodents, as well as investigated its impact on fibrinolysis, inflammation, and coagulation. An experimental setup for thrombophlebitis was established in rodents via modified ligation technique. Five groups comprised the animals: sham operation group, model group, and three Mailuoning treatment groups (low, medium, and high dosages). The pain response, edema, coagulation parameters (PT, APTT, TT, FIB), serum inflammatory markers (IL-6, TNF-α, CRP), and expression levels of endothelial markers (ICAM-1, VCAM-1, NF-κB) were evaluated. Blood flow and vascular function were further assessed by measuring hemorheological parameters and the concentrations of TXB2, ET, and 6-k-PGF1α. In contrast to the sham group, model group demonstrated statistically significant increases in endothelial expression levels, coagulation latencies, and inflammatory markers (p < 0.05). The administration of mailing, specifically at high and medium dosages, resulted in a substantial reduction in inflammatory markers, enhancement of coagulation parameters, suppression of ICAM-1 and VCAM-1 expression, and restoration of hemorheological measurements to baseline (p < 0.05). Significantly higher concentrations of 6-k-PGF1α and lower levels of TXB2 and ET were observed in high-dose group, suggesting that pro- and anti-thrombotic factors were restored to equilibrium. Utilization of Mailuoning injection in rat model of thrombophlebitis exhibited significant therapeutic impact. This effect was manifested through pain alleviation, diminished inflammation, enhanced blood viscosity and facilitation of fibrinolysis. The study indicated that Mailuoning injection may serve as a viable therapeutic option for thrombophlebitis, potentially aiding in the improvement of wound healing by virtue of its anti-inflammatory and blood flow-enhancing characteristics.

PROMETHAZINE-INDUCED THROMBOPHLEBITIS IN A NIGERIAN MAN: A CASE REPORT.

Introduction: Promethazine is a phenothiazine derivative that possesses antihistamine, anti-dopaminergic and anticholinergic properties. It is commonly used to treat motion sickness, allergic conditions, nausea and vomiting, in addition to its use as a sedative. Promethazine has vesicant properties and is highly caustic to the intima of blood vessels and surrounding tissues. Intravenous administration may result in thrombophlebitis, unintentional intra-arterial administration, perivascular extravasation and tissue necrosis. To the best of our knowledge there is no previous published report of promethazine-induced thrombophlebitis from sub- Saharan Africa. Case Report: A 29-year-old Nigerian male was admitted at our hospital on account of malaria with acute gastroenteritis. Due to persistent vomiting, he was administered 25 mg of promethazine injection via a size 22G intravenous cannula which was inserted the previous day on the anteromedial aspect of his right forearm and maintained with continuous intravenous crystalloid infusion. Upon administration of promethazine, he experienced intense burning and erythema. The cannula was removed immediately, another cannula was inserted on the contralateral arm, and promethazine was replaced with ondansetron. Subsequently, he developed a tender, subcutaneous cord-like swelling extending from the middle-third of the anteromedial aspect of his right forearm, corresponding with the site of previous venous cannulation. Ultrasonography revealed a hypoechoic, non-compressible basilic vein, with no flow on colour Doppler interrogation, in keeping with superficial thrombophlebitis. He was treated with a topical anti-inflammatory agent, and the pain and redness subsided after four weeks. Conclusion: The preferred parenteral route of administration of promethazine is deep intramuscular injection. Recommendations to prevent promethazine-induced thrombophlebitis include: use of large and patent veins, use of lower doses, drug dilution and slow administration, use of alternative therapies, and patient education. Promethazine-induced tissue injury is under-reported in this part of the world. Creating awareness through this case report would help reduce the morbidity following promethazine administration.

[Bacterial Meningitis and Suppurative Thrombophlebitis after Trigger Point Injections: A Case Report].

A 73-year-old woman with untreated diabetes mellitus visited our emergency department with a 4-day history of progressive headache, fever, and chills. She received trigger point injections (TPI) into the right sternocleidomastoid for exercise-induced ipsilateral shoulder pain, 13 days before admission and into the right trapezius, 6 days before admission. Cerebrospinal fluid (CSF) evaluation revealed pleocytosis with a predominance of neutrophils, as well as elevated protein and reduced glucose levels. Magnetic resonance imaging of the cervical spine revealed inflammatory changes of the right-sided posterior cervical muscles and the right vertebral arch of the C5-C6 vertebrae without contrast enhancement of the right posterior cervical veins. She was diagnosed with bacterial meningitis and suppurative thrombophlebitis, and empiric broad-spectrum antibiotic therapy was administered intravenously. The initial blood culture yielded Streptococcus intermedius; however, CSF culture showed no growth. She recovered completely after a 4-week course of intravenously administered ampicillin and was discharged with oral clindamycin to complete a total 6-week antibiotic course. TPI are widely used as a safe therapeutic strategy associated with few complications, and serious infections are rare. However, clinicians must remain mindful of the possibility of these complications in immunocompromised patients, such as those with diabetes mellitus who undergo TPI. (Received September 18, 2020; Accepted December 21, 2020; Published June 1, 2021).

Assessment of a topical product based on polysulfated galactosaminoglycan as an adjuvant in the treatment of acute STP and stasis dermo-hypodermitis.

BACKGROUND: Superficial thrombophlebitis (STP) is a relatively frequent pathology characterized by possible extension to the deep venous circulation, with notable local inflammatory reaction which is treated by subcutaneous administration of Fondaparinux. Stasis dermo-hypodermitis is characterized by cutaneous hyperpigmentation and eczema, treatment for which consists of the use of drugs targeting endothelial cells (mesoglycan, FFPM, sulodexide). In this study we evaluated the impact of local application of a mixture of semi-synthetic polysulfated galactosaminoglycans on the regression rate of STP and dermo-hypodermitis in patients treated with best medical therapy (BMT). METHODS: Thirty patients (20 F and 10 M) were enrolled from May to December 2017, 20 with dermo-hypodermitis due to stasis secondary to post-thrombotic syndrome (PTS) and 10 with acute STP of the great saphenous vein or its collaterals. Topical administration of the galactosaminoglycan-based product was added to the BMT of 10 pts with PTS and 5 pts with STP for 45-60 days. In all patients a Visual Analogical Scale (VAS) was used to assess the intensity of spontaneous and induced pain at 0, 15, 30, 45 and 60 days. RESULTS: With regard to PTS, VAS values at time 0 were comparable between the two groups, while at later times there was a progressive reduction in the score, with values of ≤2 at 30 days for patients treated with the topical product based on galactosaminoglycans vs. 60 days for the other control subjects. With regard to STP, the values of VAS at time 0 between the two groups were comparable, while at time 15 the VAS value was lower in subjects treated with the topical product. CONCLUSIONS: This pilot study on the efficacy of a local formulation of a mixture of semi-synthetic polysulfated galactosaminoglycans highlighted the role of this product in accelerating the recovery of patients at the most advanced stages of chronic venous disease (CVD) and in the management of its complications. In the future, studies of larger series will be needed with the use of placebo to substantiate their effectiveness in these conditions and in other classes of CVD.

Treatment for superficial thrombophlebitis of the leg.

BACKGROUND: The optimal treatment of superficial thrombophlebitis (ST) of the legs remains poorly defined. While improving or relieving the local painful symptoms, treatment should aim at preventing venous thromboembolism (VTE), which might complicate the natural history of ST. This is the third update of a review first published in 2007. OBJECTIVES: To assess the efficacy and safety of topical, medical, and surgical treatments for ST of the leg in improving local symptoms and decreasing thromboembolic complications. SEARCH METHODS: For this update, the Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register (March 2017), CENTRAL (2017, Issue 2), and trials registries (March 2017). We handsearched the reference lists of relevant papers and conference proceedings. SELECTION CRITERIA: Randomised controlled trials (RCTs) evaluating topical, medical, and surgical treatments for ST of the legs that included people with a clinical diagnosis of ST of the legs or objective diagnosis of a thrombus in a superficial vein. DATA COLLECTION AND ANALYSIS: Two authors assessed the trials for inclusion in the review, extracted the data, and assessed the quality of the studies. Data were independently extracted from the included studies and any disagreements resolved by consensus. We assessed the quality of the evidence using the GRADE approach. MAIN RESULTS: We identified three additional trials (613 participants), therefore this update considered 33 studies involving 7296 people with ST of the legs. Treatment included fondaparinux; rivaroxaban; low molecular weight heparin (LMWH); unfractionated heparin (UFH); non-steroidal anti-inflammatory drugs (NSAIDs); compression stockings; and topical, intramuscular, or intravenous treatment to surgical interventions such as thrombectomy or ligation. Only a minority of trials compared treatment with placebo rather than an alternative treatment and many studies were small and of poor quality. Pooling of the data was possible for few outcomes, and none were part of a placebo-controlled trial. In one large, placebo-controlled RCT of 3002 participants, subcutaneous fondaparinux was associated with a significant reduction in symptomatic VTE (risk ratio (RR) 0.15, 95% confidence interval (CI) 0.04 to 0.50; moderate-quality evidence), ST extension (RR 0.08, 95% CI 0.03 to 0.22; moderate-quality evidence), and ST recurrence (RR 0.21, 95% CI 0.08 to 0.54; moderate-quality evidence) relative to placebo. Major bleeding was infrequent in both groups with very wide CIs around risk estimate (RR 0.99, 95% CI 0.06 to 15.86; moderate-quality evidence). In one RCT on 472 high-risk participants with ST, fondaparinux was associated with a non-significant reduction of symptomatic VTE compared to rivaroxaban 10 mg (RR 0.33, 95% CI 0.03 to 3.18; low-quality evidence). There were no major bleeding events in either group (low-quality evidence). In another placebo-controlled trial, both prophylactic and therapeutic doses of LMWH (prophylactic: RR 0.44, 95% CI 0.26 to 0.74; therapeutic: RR 0.46, 95% CI 0.27 to 0.77) and NSAIDs (RR 0.46, 95% CI 0.27 to 0.78) reduced the extension (low-quality evidence) and recurrence of ST (low-quality evidence) in comparison to placebo, with no significant effects on symptomatic VTE (low-quality evidence) or major bleeding (low-quality evidence). Overall, topical treatments improved local symptoms compared with placebo, but no data were provided on the effects on VTE and ST extension. Surgical treatment combined with elastic stockings was associated with a lower VTE rate and ST progression compared with elastic stockings alone. However, the majority of studies that compared different oral treatments, topical treatments, or surgery did not report VTE, ST progression, adverse events, or treatment adverse effects. AUTHORS' CONCLUSIONS: Prophylactic dose fondaparinux given for 45 days appears to be a valid therapeutic option for ST of the legs for most people. The evidence on topical treatment or surgery is too limited and does not inform clinical practice about the effects of these treatments in terms of VTE. Further research is needed to assess the role of rivaroxaban and other direct oral factor-X or thrombin inhibitors, LMWH, and NSAIDs; the optimal doses and duration of treatment in people at various risk of recurrence; and whether a combination therapy may be more effective than single treatment. Adequately designed and conducted studies are required to clarify the role of topical and surgical treatments.

Initial management and outcomes after superficial thrombophlebitis: The Cardiovascular Research Network Venous Thromboembolism study.

Although superficial thrombophlebitis (SVTE) is generally considered a benign, self-limited disease, accumulating evidence suggests that it often leads to more serious forms of venous thromboembolism. We reviewed the medical charts of 329 subjects with SVTE from the Cardiovascular Research Network Venous Thromboembolism cohort study to collect information on the acute treatment of SVTE and subsequent diagnosis of deep venous thrombosis within 1 year. All participants received care within Kaiser Permanente Northern California, a large, integrated healthcare delivery system. Fourteen (4.3%) subjects with SVTE received anticoagulants, 148 (45.0%) were recommended antiplatelet agents or nonsteroidal anti-inflammatory drugs, and in 167 (50.8%) there was no documented antithrombotic therapy. In the year after SVTE diagnosis, 19 (5.8%) patients had a subsequent diagnosis of a deep venous thrombosis or pulmonary embolism. In conclusion, clinically significant venous thrombosis within a year after SVTE was uncommon in our study despite infrequent use of antithrombotic therapy. Journal of Hospital Medicine 2016;11:432-434. © 2016 Society of Hospital Medicine.

Treatment for superficial infusion thrombophlebitis of the upper extremity.

BACKGROUND: Although superficial thrombophlebitis of the upper extremity represents a frequent complication of intravenous catheters inserted into the peripheral veins of the forearm or hand, no consensus exists on the optimal management of this condition in clinical practice. OBJECTIVES: To summarise the evidence from randomised clinical trials (RCTs) concerning the efficacy and safety of (topical, oral or parenteral) medical therapy of superficial thrombophlebitis of the upper extremity. SEARCH METHODS: The Cochrane Vascular Group Trials Search Co-ordinator searched the Specialised Register (last searched April 2015) and the Cochrane Register of Studies (2015, Issue 3). Clinical trials registries were searched up to April 2015. SELECTION CRITERIA: RCTs comparing any (topical, oral or parenteral) medical treatment to no intervention or placebo, or comparing two different medical interventions (e.g. a different variant scheme or regimen of the same intervention or a different pharmacological type of treatment). DATA COLLECTION AND ANALYSIS: We extracted data on methodological quality, patient characteristics, interventions and outcomes, including improvement of signs and symptoms as the primary effectiveness outcome, and number of participants experiencing side effects of the study treatments as the primary safety outcome. MAIN RESULTS: We identified 13 studies (917 participants). The evaluated treatment modalities consisted of a topical treatment (11 studies), an oral treatment (2 studies) and a parenteral treatment (2 studies). Seven studies used a placebo or no intervention control group, whereas all others also or solely compared active treatment groups. No study evaluated the effects of ice or the application of cold or hot bandages. Overall, the risk of bias in individual trials was moderate to high, although poor reporting hampered a full appreciation of the risk in most studies. The overall quality of the evidence for each of the outcomes varied from low to moderate mainly due to risk of bias and imprecision, with only single trials contributing to most comparisons. Data on primary outcomes improvement of signs and symptoms and side effects attributed to the study treatment could not be statistically pooled because of the between-study differences in comparisons, outcomes and type of instruments to measure outcomes.An array of topical treatments, such as heparinoid or diclofenac gels, improved pain compared to placebo or no intervention. Compared to placebo, oral non-steroidal anti-inflammatory drugs reduced signs and symptoms intensity. Safety issues were reported sparsely and were not available for some interventions, such as notoginseny creams, parenteral low-molecular-weight heparin or defibrotide. Although several trials reported on adverse events with topical heparinoid creams, Essaven gel or phlebolan versus control, the trials were underpowered to adequately measure any differences between treatment modalities. Where reported, adverse events with topical treatments consisted mainly of local allergic reactions. Only one study of 15 participants assessed thrombus extension and symptomatic venous thromboembolism with either oral non-steroidal anti-inflammatory drugs or low-molecular-weight heparin, and it reported no cases of either. No study reported on the development of suppurative phlebitis, catheter-related bloodstream infections or quality of life. AUTHORS' CONCLUSIONS: The evidence about the treatment of acute infusion superficial thrombophlebitis is limited and of low quality. Data appear too preliminary to assess the effectiveness and safety of topical treatments, systemic anticoagulation or oral non-steroidal anti-inflammatory drugs.

The extremes in orthopaedics! Whom to blame?

Traditional medicines especially the herbal paste is routinely prescribed by the herb sellers. The unsupervised combinations and preparations are easily available in our part of world. The demand and supply of such irrational combination is only based on the principle that anything natural is safe. Drugs and preparations made by the people who lack the scientific knowledge of traditional herbal medicines adversely affect the consumer. We put forward few complications that resulted after herbal paste application in those who already had visited the specialist but opted the easily available unsupervised herbal preparations.

Prevention of venous thrombosis and thrombophlebitis in long-haul flights with pycnogenol.

The aim of this study was to evaluate the occurrence of deep venous thrombosis (DVT) and superficial vein thrombosis (SVT) and its prophylaxis with an oral anti-edema and antithrombotic agent (Pycnogenol, Horphag, Research Management SA, Geneva, Switzerland) in long-haul flights, in subjects at moderate to high-risk of DVT and SVT. The study pre-included 244 pre-selected subjects; 211 were included (33 were excluded for several reasons due to logistic problems) and 198 completed the study; 13 subjects were lost for follow-up at the end of the flight, all for non-medical problems (i.e., for difficult connections). All subjects were scanned within 90 minutes before the flight and within 2 hours after disembarking. Subjects were supplemented with 100 mg Pycnogenol per capsule. Treatment subjects received two capsules between 2 and 3 hours before flights with 250 mL of water; two capsules were taken 6 hours later with 250 mL of water and one capsule the next day. The control group received comparable placebo at the same intervals. The flight duration was on average 8 hours and 15 minutes (SD 55 min) (range, 7.45-12.33). In the control group there were five thrombotic events (one DVT and four superficial thromboses) while only nonthrombotic, localized phlebitis was observed in the Pycnogenol group (5.15% vs. no events; p<0.025). The ITT (intention to treat) analysis detects 13 failures in the control group (eight lost to follow up + five thrombotic events) of 105 subjects (12.4%) vs. five failures (4.7%; all lost, no thrombotic events) in the treatment group (p<0.025). No unwanted effects were observed. In conclusion, this study indicates that Pycnogenol treatment was effective in decreasing the number of thrombotic events (DVT and SVT) in moderate-to-high risk subjects, during long-haul flights.

Outpatient treatment of deep venous thrombosis: a clinical care pathway managed by the emergency department.

STUDY OBJECTIVE: We evaluate the effectiveness and safety of an outpatient clinical care pathway for the initial treatment of acute proximal lower-extremity deep venous thrombosis (DVT) with low molecular weight heparin (LMWH) managed by the emergency department of 2 affiliated community hospitals. METHODS: This observational, retrospectively defined, population-based study with 39(1/2) months of preintervention analysis and 32(1/2) months of postintervention analysis was conducted in 2 suburban EDs of a large group model health maintenance organization. Our outpatient DVT clinical care pathway used careful patient selection and multidisciplinary follow-up. Ninety-six patients before the intervention and 178 patients after the intervention met eligibility criteria for the pathway. Adverse events during the first 2 weeks of treatment included symptomatic pulmonary embolism (PE), progressive DVT, minor and major bleeding, and death. RESULTS: Demographic and baseline clinical characteristics of the 2 groups were similar. Five (5.2%) of 96 preintervention subjects (95% confidence interval [CI] 2.4 to 8.1) developed adverse events compared with 5 (2.8%) of 178 postintervention subjects (95% CI 1.5 to 4.1; difference between groups 2.4%; P =.50). In each group, 1 (1.0% versus 0.6%) subject developed a PE, 2 (2.1% versus 1.1%) developed progressive symptoms of progressive DVT, and 2 (2.1% versus 1.1%) developed minor bleeding. Major bleeding occurred in 1 (1.0%) preintervention subject and no postintervention subjects. No patient in either cohort died. CONCLUSION: Managed by the ED, an outpatient DVT clinical care pathway using careful patient selection and an integrated multidisciplinary approach can provide a similar degree of effectiveness and safety as customary inpatient therapy.

Pharmacokinetics of tissue plasminogen activator in an isolated extracorporeal circuit.

PURPOSE: The aim of this study was to investigate the pharmacokinetics of tissue plasminogen activator (tPA) under the conditions of an isolated extracorporeal circuit. METHODS: Plasma levels of tPA were measured in the perfusion solution and in central venous blood before, during, and after the perfusion in seven patients undergoing regional hyperthermic fibrinolytic perfusion with tPA in addition to surgical thrombectomy for extended deep venous thrombosis. RESULTS: After 15 minutes of fibrinolytic perfusion, the level of tPA in the perfusion solution was 10,427 +/- 4432 ng/mL, and after 30 minutes the maximum level of 19,726 +/- 5630 ng/mL was reached. After 60 minutes when the perfusion was discontinued, tPA concentrations dropped to 15,931 +/- 4818 ng/mL. In central venous blood, tPA levels increased to a maximum of 230.7 +/- 89.6 ng/mL after 60 minutes of perfusion, which represented 1.4% of the concentration measured in the perfusion solution at the same time. With disconnection of the extracorporeal circuit, the tPA levels in central venous blood decreased rapidly and reached a level of 24.1 +/- 8.7 ng/mL after 120 minutes. CONCLUSION: The use of regional hyperthermic fibrinolytic perfusion in the treatment of extended deep venous thrombosis makes it possible to achieve extremely high concentrations of tPA in the perfusion solution. At the same time, the entry of the fibrinolytic agent into the systemic circulation is minimized.

Treatment of superficial vein thrombophlebitis of the arm with Essaven gel--a placebo-controlled, randomized study.

The aim of this randomized, placebo-controlled study was to evaluate the effect of local treatment with Essaven gel (EG), in comparison with placebo and with a group of controls in 23 patients with superficial vein thrombophlebitis (SVTPH) of the arms. SVTPH was consequent to infusional treatment with an intravenous catheter. The 4-week study evaluated the average skin temperature and an analogue symptomatic score. In patients treated with active EG, the decrease in score and in composite skin temperature was significantly larger than in the placebo and control groups. No intolerance was observed. The decrease in score and temperature in the placebo group was mainly due to skin manipulation and massage and to spontaneous resolution. In conclusion treatment with EG in arm SVTPH improves signs /symptoms and decreases skin temperature faster. This study confirms earlier observations on the effective, local use of EG in SVTPH.

[Lowering high levels of fasting total homocysteine with folic acid and vitamins B in patients with venous thromboembolism: relationship between response and the C677T methylenetetrahydrofolate reductase (MTHRF) genotype]. / Reducción de concentraciones elevadas de homocisteína con ácido fólico y vitaminas B en pacientes con tromboembolia venosa: relación entre respuesta y genotipo C677T de la metilén tetrahidrofólico reductasa (MTHFR).

BACKGROUND: High levels of plasma total homocysteine (tHcy) are involved in arterial or venous occlusive diseases. It essentially depends on the nutritional status of folic acid (FA) and vitamins B12 or B6, but also on the methylenetetrahydrofolate reductase (MTHFR) enzymatic activity. We aim to evaluate the response of the hyperhomocysteinemia (HHcy) to a standard schedule of vitamin supplementation, according with the MTHFR genotype. PATIENTS AND METHODS: 227 patients, diagnosed with venous thromboembolism (VTE) were analysed for tHcy (in fasting conditions), and for the MTHFR-C677T gene polymorphism. When the tHcy exceeded the cut-off point (men = 16, women = 15 mumol/l), the patients were supplemented with a dose equivalent to 1 mg FA, 0.2 mg B12 and 100 mg of B6, daily by 6 weeks. Afterwards they were reanalysed and the reduction was stratified by MTHFR genotype, looking for any difference in the response. RESULTS: The mean fasting tHcy was 12.3 mumol/l (SD = 8). The 51 hyperhomocysteinemic patients (22%) were older (65.1 y) than the normal ones (55.0 y) (p = 0.0001). The treatment was carried out properly in 46 patients (90%). The pre-treatment mean Hcy was 23.2 (SD = 10.5) mumol/l, and it was reduced to 13.0 (SD = 5.9) (p = 0.0001) (mean reduction = 42.1%). By genotype, the C/C reduced from 21.0 to 13.2 mumol/l (37%) (n = 18), the C/T from 25.0 to 12.6 mumol/l (46%) (n = 24), and the abnormal homozygotes T/T from 22.7 to 14.5 mumol/l (39%) (n = 4), although no statistical significant differences were found. In 80% of cases (37/46), tHcy values normalised. A negative correlation (r = -0.471) (p = 0.005) was observed between age and response. CONCLUSIONS: The FA/B6/B12 based therapy reduces in a simple, quick and effective way (> 40% in 6 weeks) the pathologic tHcy levels on a VTE population and this is not influenced by the MTHFR genotype. As HHcy seems related with recurrences of venous thrombosis, we could speculate if it would be useful to analyse routinely the tHcy, attempting reduction in selected cases.

[Case report of acute intoxication from intravenous injection of petroleum] . / A propos d'un cas d'intoxication aiguë par injection intraveineuse directe de pétrole.

A 18-year-old patient injected intravenously 2.5 mL of paraffin oil into the right upper limb. It caused a local thrombophlebitis with a slow evolution. A collapsus occurred on the sixth day. The authors obtained a clinical recovery of the limb after heparine and oral anticoagulation.

Antithrombotic effects of BCH 2763, a new direct thrombin inhibitor, in a canine model of venous thrombosis.

Deep venous thrombosis (DVT) is a common cardiovascular disease, resulting in significant mortality each year in the United States. Direct thrombin inhibitors represent a new class of drugs that could potentially be better than conventional antithrombotic therapy based on indirect inhibition of coagulation factors with heparin and warfarin. BCH 2763 is a potent, selective bifunctional thrombin inhibitor that blocks both the active catalytic site and the anion binding exosite. The objective of this study is to test the antithrombotic efficacy of BCH 2763 in a canine model of DVT induced through electrolytic injury to the femoral vein. BCH 2763 was administered at three dose levels: 0.125 mg/kg bolus followed by 10 microg/kg/min IV infusion (low-dose; n = 5), 0.25 mg/kg bolus followed by 20 microg/kg/min infusion (mid-dose; n = 5), and 0.75 mg/kg bolus followed by 60 microg/kg/min (high-dose; n = 5). The control group (n = 5) received a 5-ml intravenous bolus of saline followed by a 1 mL/kg/h infusion. The parameters evaluated were changes in activated partial thromboplastin time (aPTT), thrombin time (TT), prothrombin time (PT), time to formation of an occlusive thrombus in the femoral vein, and the amount of venous blood flow delivered over the course of the experiment. There were significant dose-dependent increases in aPTT, TT, and PT in the BCH 2763-treated animals compared with the control group. The time to formation of an occlusive thrombus in the control group averaged 69.6 +/- 9 minutes. Treatment with BCH 2763 prolonged the time to occlusion to 126.4 +/- 13 minutes in the low-dose group, 155.4 +/- 17 minutes in the mid-dose group, and 229 +/- 7 minutes in the high-dose group (80% remained patent for the duration of the study), which were all significantly greater than the controls. Femoral venous blood flow was significantly greater in the mid-dose (51 +/- 8%) and the high-dose (70 +/- 6%) groups compared with the control vessels (22 +/- 3%). In conclusion, the results of this study indicate that BCH 2763 is an effective intravenous antithrombotic agent in the canine electrolytic injury model of venous thrombosis.

Pharmacokinetics and pharmacodynamics of melagatran, a novel synthetic LMW thrombin inhibitor, in patients with acute DVT.

Forty-eight patients with acute proximal deep vein thrombosis (DVT) were randomised to intravenous infusions for 4 to 6 days with melagatran, a novel synthetic low molecular weight thrombin inhibitor, or unfractionated heparin adjusted by the activated partial thromboplastin time (APTT). The aim of the study was to investigate the pharmacokinetics, pharmacodynamics and the safety of melagatran therapy at three different doses. Steady-state plasma concentrations were rapidly achieved and maintained throughout the infusion period. The mean plasma concentrations in the low, medium and high dose groups were 0.17, 0.31 and 0.53 micromol/l, respectively. The prolongation of APTT was stable during the melagatran infusions and correlated to the plasma concentration. Phlebographically verified regression of thrombus size measured as decrease in Marder score was seen after 4 to 6 days in 8 of 12 patients, 6 of 12 patients and 5 of 11 patients in the low, medium and high dose groups of melagatran and in 5 of the heparin-treated patients. In the low dose group with melagatran, thrombus extension was seen in one patient. At the dose levels studied, melagatran was well tolerated with no clinically significant bleeding problems, suggesting that melagatran could safely be given to patients suffering from DVT.

A model for collaboration in quality improvement projects: implementing a weight-based heparin dosing nomogram across an integrated health care delivery system.

BACKGROUND: At Aurora Health Care, an integrated delivery system based in Milwaukee, a system-level clinical quality improvement department was established in 1995 to facilitate collaboration on clinical quality improvement (QI) initiatives. THE COLLABORATIVE MODEL: A model was developed to use expertise within the system and avoid unnecessary duplication of efforts, while maintaining buy-in for the project's interventions at the point of service delivery. It was believed that a single team could design the improvement efforts or guidelines, and then work at a more local level with a different group of people to implement the processes. APPLYING THE MODEL TO THE HEPARIN QI PROJECT: Anticoagulation with heparin is considered the mainstay of treatment for pulmonary embolism and deep venous thrombosis. However, a large gap was found between present anticoagulation practices and published best practice in regards to achieving a key process measure. To reduce the overall time to achieving effective anticoagulation, a system-level team created an intervention primarily consisting of a preprinted order sheet, including the weight-based heparin dosing nomogram, and an education plan for physicians and other health care professionals. Significant improvement was observed at all pilot sites with overall rates of adequate anticoagulation within the first 24 hours improving from 73% to 95%. DISCUSSION: The system was able to standardize care at four of its five major hospitals and provide for better patient outcomes to a larger segment of the community, and then to replicate the heparin project to four additional sites during a six-month period. This model has been successfully applied to other quality improvement projects.