Aim. This study was designed to examine the possible role of high-dose intravenous methylprednisolone (IVMP) in the development of venous thrombosis (VT). The cerebral one anecdotally had been reported in patients with r...Aim. This study was designed to examine the possible role of high-dose intravenous methylprednisolone (IVMP) in the development of venous thrombosis (VT). The cerebral one anecdotally had been reported in patients with relapsing remitting multiple sclerosis (RRMS) in acute attacks and the possible preventive role of enoxaparin. Material and Methods. From a pool of 520 patients, 388 patients with definite RRMS who fulfilled entry characteristics were selected and randomly received either a 5-day course of daily 1 gr IVMP or the aforementioned plus 5 days of daily subcutaneous 40 units of enoxaparin according to a predefined protocol. Results. Mean age, gender ratio, mean relapse rate, and EDSS were similar in both groups of patients (P > 0.05). Finally, 366 patients remained in the study. Of 188 patients treated with IVMP with 855 relapses, 5 developed VT (0.37% per patient per year and 0.58% per each course of IVMP) within 3 to 15 days of starting therapy. None of the 178 patients who experienced 809 relapses who received IVMP plus enoxaparin developed such complications. Conclusion. The study implies that high-dose IVMP in MS exacerbation may increase the risk of VT and prophylactic anticoagulant treatment in this setting is warranted.
Ultra-low-dose aspirin has shown a prothrombotic effect in the laser-induced thrombosis model. Several studies of our laboratory have shown a positive effect in rats with two different experimental models of portal hyper...Ultra-low-dose aspirin has shown a prothrombotic effect in the laser-induced thrombosis model. Several studies of our laboratory have shown a positive effect in rats with two different experimental models of portal hypertension: portal vein ligation, a model with an almost normal liver, and 30 days of bile duct ligation, a model with cirrhosis and presence of ascitis. In both models of portal hypertensive rats, bleeding time was prolonged and thrombi formation, in a laser-induced model of thrombi production, decreased. The hypotheses of the presented studies were that ultra-low-dose aspirin could decrease the bleeding complications in these models and that the mechanism for these effects could act thorough the COX pathway. In different studies, ultra-low dose of aspirin normalized the induced hemorrhage time, thrombi production, and platelet-endothelial cell interaction. The possible beneficial role of these doses of aspirin and mechanism of COX 2 inhibition are discussed.
Acetyl salicylic acid (ASA) is widely used in clinical practice. Previous studies done in rats showed unexpected thrombotic potencies of this drug used at ultra-low doses. This review is the first report in which the eff...Acetyl salicylic acid (ASA) is widely used in clinical practice. Previous studies done in rats showed unexpected thrombotic potencies of this drug used at ultra-low doses. This review is the first report in which the effects of a wide range of ASA concentration on a microvessel model of laser-induced thrombus formation and Induced Hemorrhagic Time in animals were largely studied.
Cardiovascular disease (CVD), principally heart disease and stroke, is the leading cause of death for both males and females in developed countries. Aspirin is the most widely used and tested antiplatelet drug in CVD, an...Cardiovascular disease (CVD), principally heart disease and stroke, is the leading cause of death for both males and females in developed countries. Aspirin is the most widely used and tested antiplatelet drug in CVD, and it is proven to be the cornerstone of antiplatelet therapy in treatment and prevention of CVD in clinical trials in various populations. In acute coronary syndrome, thrombotic stroke, and Kawasaki's disease, acute use of aspirin can decrease mortality and recurrence of cardiovascular events. As secondary prevention, aspirin is believed to be effective in acute coronary syndrome, stable angina, revascularization, stroke, TIA, and atrial fibrillation. Aspirin may also be used for patients with a high risk of future CVD for primary prevention, but the balance between benefits and the possibility of side effects must be considered.
Antiplatelet therapy has been documented to reduce risks of cardiovascular disease after acute myocardial infarction, coronary artery bypass graft, and in chronic atrial fibrillation patients, amongst other risk factors....Antiplatelet therapy has been documented to reduce risks of cardiovascular disease after acute myocardial infarction, coronary artery bypass graft, and in chronic atrial fibrillation patients, amongst other risk factors. Conventional management of thrombosis-based disorders includes the use of heparin, oral anticoagulants, and the preferred antiplatelet agent aspirin. Interestingly, aspirin was not intended to be used as an antiplatelet agent; rather, after being repurposed, it has become one of the most widely prescribed antithrombotic drugs. To this end, there have been several milestones in the development of antiplatelet agents in the last few decades, such as adenosine diphosphate receptor inhibitors, phosphodiesterase inhibitors, and GPIIb/IIIa inhibitors. However, given some of the limitations of these therapies, aspirin continues to play a major role in the management of thrombotic and cardiovascular disorders and is expected to do so for years to come.
Platelet activation has been implicated in microvascular thrombosis and organ failure in critically ill patients. In the first part the present paper summarises important data on the role of platelets in systemic inflamm...Platelet activation has been implicated in microvascular thrombosis and organ failure in critically ill patients. In the first part the present paper summarises important data on the role of platelets in systemic inflammation and sepsis as well as on the beneficial effects of antiplatelet drugs in animal models of sepsis. In the second part the data of retrospective and prospective observational clinical studies on the effect of aspirin and other antiplatelet drugs in critically ill patients are reviewed. All of these studies have shown that aspirin and other antiplatelet drugs may reduce organ failure and mortality in these patients, even in case of high bleeding risk. From the data reviewed here interventional prospective trials are needed to test whether aspirin and other antiplatelet drugs might offer a novel therapeutic option to prevent organ failure in critically ill patients.
Postthrombotic syndrome (PTS) is a late outcome of deep vein thrombosis characterized by cramping pain, swelling, hyperpigmentation, eczema, lipodermatosclerosis, and ulceration in the leg due to increased venous outflow...Postthrombotic syndrome (PTS) is a late outcome of deep vein thrombosis characterized by cramping pain, swelling, hyperpigmentation, eczema, lipodermatosclerosis, and ulceration in the leg due to increased venous outflow resistance and reflux venous flow. Newer surgical and endovascular interventions have a promising result in the management of postthrombotic syndrome. Early surgical or endovascular interventions in appropriately selected patients may decrease the incidence of recurrent ulceration and skin changes and provide a better quality of life. Duplex and IVUS (intravenous ultrasound) along with venography serve as cornerstone investigative tools for assessment of reflux and obstruction. Venous obstruction, if present, should be addressed earlier than reflux. It requires endovenous stenting, endophlebectomy, or open bypass procedures. Venous stripping, foam sclerotherapy, radiofrequency, or laser ablation are used to abolish superficial venous reflux. Valvuloplasty procedures are useful for incompetent but intact deep venous valves, while transposition or axillary vein autotransplantation is done for completely destroyed valves.
2-5% of patients undergoing hip or knee arthroplasty develop a symptomatic DVT; there is evidence to suggest that without prophylaxis 40-60% of patients have a subclinical DVT. This can be reduced by around half with app...2-5% of patients undergoing hip or knee arthroplasty develop a symptomatic DVT; there is evidence to suggest that without prophylaxis 40-60% of patients have a subclinical DVT. This can be reduced by around half with appropriate thromboprophylaxis; there still remains a significant incidence of subclinical DVT. Therefore, it is important to know, as orthopaedic surgeons, if our patients undergoing large joint arthroplasty are being adversely affected. Post-thrombotic syndrome (PTS) is usually associated with symptomatic DVT, and the purpose of this paper is to address if asymptomatic DVT is also associated with an increased risk of PTS. The majority of evidence gathered does not support a link; therefore, there is no evidence to warrant a change in practice to warn patients of a potential risk or to routinely screen asymptomatic patients.
Thirty-two consecutive children aged 0-18 years with VTE treated with LMWH administered as a continuous infusion (CI) were identified at the Children's University Hospital Brno. The treatment led to at least partial reso...Thirty-two consecutive children aged 0-18 years with VTE treated with LMWH administered as a continuous infusion (CI) were identified at the Children's University Hospital Brno. The treatment led to at least partial resolution of the thrombus within two weeks in 85% of patients. There were no adverse events or increased bleeding reported in any patients. No recurrences were observed during a followup period of 6 months. Although continuous infusion should not replace subcutaneous (SC) administration of LMWH, CI appeared to be safe and efficient and may provide an alternate method of administering LMWH in a subset of the paediatric population where SC administration may not be feasible. Further prospective studies are needed to support the promising findings of our pilot clinical observation.
Deep vein thrombosis is a common condition that is often difficult to diagnose and may be lethal when allowed to progress. However, early implementation of treatment substantially improves the disease prognosis. Therefor...Deep vein thrombosis is a common condition that is often difficult to diagnose and may be lethal when allowed to progress. However, early implementation of treatment substantially improves the disease prognosis. Therefore, care must be taken to both acquire an accurate differential diagnosis for patients with symptoms as well as to screen at-risk asymptomatic individuals. Many diagnostic tools exist to evaluate deep vein thrombosis. Compression ultrasonography is currently the most effective diagnostic tool in the emergency department, shown to be highly accurate at minimal expense. However, limited availability of ultrasound technicians may result in delayed imaging or in a decision not to image low-risk cases. Many studies support emergency physiciansas capable of accurately diagnosing deep vein thrombosis using bedside ultrasound. Further integration of ultrasound into the training of emergency physicians for use in evaluating deep vein thrombosis will improve patient care and cost-effective treatment.
We previously found that gender influenced the JAK2 V617F allele burden, but it is unknown whether this gender difference in molecular epidemiology influences complications in the myeloproliferative neoplasms (MPNs). His...We previously found that gender influenced the JAK2 V617F allele burden, but it is unknown whether this gender difference in molecular epidemiology influences complications in the myeloproliferative neoplasms (MPNs). Historically, vascular complications represented the most common cause of mortality in polycythemia vera and essential thrombocytosis and contributed to morbidity in primary myelofibrosis. To determine the influence of gender on vascular complications, we retrospectively analyzed associations between gender and vascular complications. Despite their younger age, less prevalent dyslipidemia or smoking history, lower white blood counts, and lower JAK2 V617F allele burden, women had higher rates of abdominal venous thrombosis and comparable rates of all vascular complications. Vascular risk is currently not easily stratified by MPN-disease burden or traditional risk factors. Our analysis contributes to growing literature emphasizing gender differences in the MPN and further supports the important impact of individual and host variation on MPN clinical manifestations, and especially vascular risk.
Surgery for colorectal cancer conveys a high risk of venous thromboembolism (VTE). The effect of thromboprophylactic regimens of varying duration on the incidence of VTE was assessed in 417 patients undergoing surgery be...Surgery for colorectal cancer conveys a high risk of venous thromboembolism (VTE). The effect of thromboprophylactic regimens of varying duration on the incidence of VTE was assessed in 417 patients undergoing surgery between 2005 and 2009 for colorectal cancer. Low-dose unfractionated heparin (LDUH) was used in 52.7% of patients, low-molecular-weight heparin (LMWH) in 35.3%, and 10.7% received LDUH followed by LMWH. Pharmacological prophylaxis was continued after hospitalisation in 31.6%. Major bleeding occurred in 4% of patients. The 30-day mortality rate was 1.9%. The incidence of symptomatic VTE from hospital admission for surgery to 12 months after was 2.4%. There were no in-hospital VTE events. The majority of events occurred in the three-month period after discharge, but there were VTE events up to 12 months, especially in patients with more advanced cancer and multiple comorbidities.
Polycythemia vera (PV) is a chronic myeloproliferative disorder whose major morbidity and mortality are thrombohaemorragic events. Current guidelines advise maintaining hematocrit (HCT) level below 45% in males and 42% i...Polycythemia vera (PV) is a chronic myeloproliferative disorder whose major morbidity and mortality are thrombohaemorragic events. Current guidelines advise maintaining hematocrit (HCT) level below 45% in males and 42% in females. Such targets lean on pathophysiological reasoning, while evidence from ECLAP and PVSG-01, the two largest prospective studies in this disease, suggests no difference in the rate of thrombosis in patients maintained at different HCT values below 50%-52%. Cytoreductive therapy in PV (CYTO-PV) is a multicenter, randomized, and controlled trial assess the benefit/risk profile of cytoreductive therapy with phlebotomy or HU aimed at maintaining HCT < 45% versus maintaining HCT in the range 45%-50%. CYTO-PV is being conducted in the framework of the Gruppo Italiano Malattie Ematologiche nell'Adulto (GIMEMA) and is funded by the Italian Drug Agency (AIFA). It is an independent trial with broad recruitment criteria to mimic clinical practice. We describe here the study and its advancement status. Conclusions. Clinical research in rare disease can be carried out with limited funds, provided a research hypothesis is felt as clinically relevant by a scientific community willing to share knowledge on the outcome of clinical practice, thus producing scientific results useful to improve treatment and prognosis of patients.
Guidelines for thromboprophylaxis in pregnancy are usually based upon clinical observations and expert opinion. For optimal impact, their use must be attended by consistency in the advice given to women. In this observat...Guidelines for thromboprophylaxis in pregnancy are usually based upon clinical observations and expert opinion. For optimal impact, their use must be attended by consistency in the advice given to women. In this observational study, we evaluated the performance of a scoring system, used as a guide for clinicians administering dalteparin to pregnant women at increased risk of venous thromboembolism. The work included 47 women treated with dalteparin prior to adoption of the scoring system and 58 women treated with dalteparin after its adoption. The indication for thromboprophylaxis was recorded in each case together with details of the regimen employed, obstetric, and haematological outcomes. The main outcome measure was to determine whether consistency improved after adoption of the scoring system. We also recorded the occurrence of any new venous thromboembolism, haemorrhage, the use of regional anaesthesia during labour, evidence of allergy, and thrombocytopenia. We found that use of the scoring system improved the consistency of advice and increased the mean duration of thromboprophylaxis. None of the subjects suffered venous thromboembolism after assessment using the scoring system. There was no increase in obstetric or anaesthetic morbidity when dalteparin was given antenatally period and no evidence of heparin-induced thrombocytopenia.
Objective. To evaluate the incidence of deep vein thrombosis in hospitalized Chinese medical patients and the impact of DVT prophylaxis. Methods. All cases of confirmed proximal DVT from 1 January 2005 to 31 December 200...Objective. To evaluate the incidence of deep vein thrombosis in hospitalized Chinese medical patients and the impact of DVT prophylaxis. Methods. All cases of confirmed proximal DVT from 1 January 2005 to 31 December 2008 were reviewed retrospectively to determine the presence of risk factors and whether DVT developed: during hospitalization in medical wards or in case of readmission with a diagnosis of DVT within 14 days of discharge from a recent admission to medical wards. The impact of prophylaxis will be estimated by comparing the annual incidence of proximal DVT among medical patients hospitalized from 2005 to 2007 with that of 2008 (DVT prophylaxis commonly used). Results. From 1 January 2005 to 31 December 2008, 3938 Doppler ultrasound studies were performed for suspected DVT. Proximal DVT was diagnosed in 687 patients. The calculated incidence of proximal DVT among medical patients hospitalized for at least two days was 1.8%, 2%, and 1.7% for the year 2005, 2006, and 2007, respectively. The incidence was 1.1% for 2008 (P < .001). Conclusion. Proximal DVT was substantial in Chinese medical patients, and DVT prophylaxis might reduce such risk.
Thrombocytosis is a commonly encountered clinical scenario, with a large proportion of cases discovered incidentally. The differential diagnosis for thrombocytosis is broad and the diagnostic process can be challenging....Thrombocytosis is a commonly encountered clinical scenario, with a large proportion of cases discovered incidentally. The differential diagnosis for thrombocytosis is broad and the diagnostic process can be challenging. Thrombocytosis can be spurious, attributed to a reactive process or due to clonal disorder. This distinction is important as it carries implications for evaluation, prognosis, and treatment. Clonal thrombocytosis associated with the myeloproliferative neoplasms, especially essential thrombocythemia and polycythemia vera, carries a unique prognostic profile, with a markedly increased risk of thrombosis. This risk is the driving factor behind treatment strategies in these disorders. Clinical trials utilizing targeted therapies in thrombocytosis are ongoing with new therapeutic targets waiting to be explored. This paper will outline the mechanisms underlying thrombocytosis, the diagnostic evaluation of thrombocytosis, complications of thrombocytosis with a special focus on thrombotic risk as well as treatment options for clonal processes leading to thrombocytosis, including essential thrombocythemia and polycythemia vera.
Patients with malignant neoplastic diseases represent a high-risk population relative to thromboembolic disease. With the advent of improved and accessible diagnostic technology, for example, ultrasound and/or spiral CT...Patients with malignant neoplastic diseases represent a high-risk population relative to thromboembolic disease. With the advent of improved and accessible diagnostic technology, for example, ultrasound and/or spiral CT scans, timely diagnosis of venous thromboembolic events (VTE) is readily accomplished. The introduction of low-molecular-weight heparin (LMWH) approximately two decades ago (in contrast to unfractionated heparin and vitamin K antagonists) has provided a class of agents with a favorable therapeutic index. In the review to follow, the literature regarding the use of LMWH in oncologic patient populations is summarized. Topics addressed include prophylaxis, and treatment as well as consideration of the potential anti-neoplastic properties of this class of drugs.
Deep vein thrombosis (DVT) and pulmonary embolism (PE) are known collectively as venous thromboembolism (VTE). Venous thromboembolic events are common and potentially life-threatening complications following trauma with...Deep vein thrombosis (DVT) and pulmonary embolism (PE) are known collectively as venous thromboembolism (VTE). Venous thromboembolic events are common and potentially life-threatening complications following trauma with an incidence of 5 to 63%. DVT prophylaxis is essential in the management of trauma patients. Currently, the optimal VTE prophylaxis strategy for trauma patients is unknown. Traditionally, pelvic and lower extremity fractures, head injury, and prolonged immobilization have been considered risk factors for VTE; however it is unclear which combination of risk factors defines a high-risk group. Modalities available for trauma patient thromboprophylaxis are classified into pharmacologic anticoagulation, mechanical prophylaxis, and inferior vena cava (IVC) filters. The available pharmacologic agents include low-dose heparin (LDH), low molecular weight heparin (LMWH), and factor Xa inhibitors. Mechanical prophylaxis methods include graduated compression stockings (GCSs), pneumatic compression devices (PCDs), and A-V foot pumps. IVCs are traditionally used in high risk patients in whom pharmacological prophylaxis is contraindicated. Both EAST and ACCP guidelines recommend primary use of LMWHs in trauma patients; however there are still controversies regarding the definitive VTE prophylaxis in trauma patients. Large randomized prospective clinical studies would be required to provide level I evidence to define the optimal VTE prophylaxis in trauma patients.
Prothrombin fragment 1+2 is excreted in urine (uF1+2) as a result of in vivo thrombin generation and can be a marker of coagulation status after an operative procedure. This study compared uF1+2 levels in patients with s...Prothrombin fragment 1+2 is excreted in urine (uF1+2) as a result of in vivo thrombin generation and can be a marker of coagulation status after an operative procedure. This study compared uF1+2 levels in patients with symptomatic and non-symptomatic venous thromboembolism (VTE) after total knee replacement (TKR) and in event-free sex- and age-matched controls. Significantly higher median uF1+2 levels were seen in the VTE patients on days 1, 3, and the day of venography (mostly day 7) after TKR compared with controls. The uF1+2 levels tended to be high in some patients with symptomatic VTE; however, the discriminatory efficacy of the test could not be evaluated. In conclusion, this study showed that patients with VTE tend to have significantly higher uF1+2 levels compared with patients without events between days 1 and 7 after TKR surgery. Measurement of uF1+2 could provide a simple, non-invasive clinical test to identify patients at risk of VTE.
Use of animal models of inherited and induced von Willebrand factor (VWF) deficiency continues to advance the knowledge of VWF-related diseases: von Willebrand disease (VWD), thrombotic thrombocytopenic purpura (TTP), an...Use of animal models of inherited and induced von Willebrand factor (VWF) deficiency continues to advance the knowledge of VWF-related diseases: von Willebrand disease (VWD), thrombotic thrombocytopenic purpura (TTP), and coronary artery thrombosis. First, in humans, pigs, and dogs, VWF is essential for normal hemostasis; without VWF bleeding events are severe and can be fatal. Second, the ADAMTS13 cleavage site is preserved in all three species suggesting all use this mechanism for normal VWF multimer processing and that all are susceptible to TTP when ADAMTS13 function is reduced. Third, while the role of VWF in atherogenesis is debated, arterial thrombosis complicating atherosclerosis appears to be VWF-dependent. The differences in the VWF gene and protein between humans, pigs, and dogs are relatively few but important to consider in the design of VWF-focused experiments. These homologies and differences are reviewed in detail and their implications for research projects are discussed. The current status of porcine and canine VWD are also reviewed as well as their potential role in future studies of VWF-related disorders of hemostasis and thrombosis.