Evidence Of Venous Thromboembolism Research Articles

A CASE REPORT ON EXTENSIVE ARTERIAL THROMBOSIS AS A COMPLICATION OF COVID-19 INFECTION

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: Coronavirus disease (COVID-19) is a global health crisis. It is associated with increased activation of the clotting system leading to thrombotic complications in 5 to 23% of cases[1]. It is known to cause significant venous thromboembolism and few cases with arterial thrombosis with increased risk of life-threatening complications like myocardial infarction, ischemic stroke, splenic infarct, and left ventricular clot have been reported[2]. CASE PRESENTATION: A 70-year-old female with a past medical history of coronary artery disease, Hypertension, COPD, recent COVID-19 (3 weeks ago) not requiring admission to hospital presented to the hospital with bilateral leg and forearm pain. Leg pain was worse with activity. She had feeble peripheral pulses on palpation.She underwent Computed Tomography angiography which showed extensive arterial thrombosis involving the distal abdominal aorta, left common iliac artery, superior mesenteric artery, and also showed an area of wedge-shaped infarction in the spleen. She had a thrombus at the apex of the left ventricle, with incidental 1.3 cm spiculated mass in the left lung. There was no evidence of venous thromboembolism in imaging.She was started on therapeutic anticoagulation with heparin. After multidisciplinary discussion with Hematology, Vascular surgery, and Cardiology, her anticoagulation was changed to Enoxaparin. She was managed medically. Workup including JAK2, beta-2 glycoprotein antibodies, lupus anticoagulant, and anticardiolipin antibodies was negative. DISCUSSION: The exact mechanisms that activate coagulation cascade in SARS-CoV-2 infection are still unknown, but they are found to be associated with increased thrombogenesis. SARS-CoV-2 viral infection can activate the plasmatic clotting system by activating multiple procoagulant pathways. Angiotensin-converting enzymes 2 are normally found on various cells such as lymphocytes, alveolar cells, monocytes/macrophages, and platelets. In SARS-CoV-2 infection, Surface S protein of SARS-CoV-2 binds to its target transmembrane receptor( ACE2 protein) and down-regulates the expression of ACE2 protein. It leads to the accumulation of angiotensin II in the body which interacts with platelets and endothelial cells leading to further promotion of clot formation[3]. This was the likely cause of hypercoagulable state in our patient leading to thrombosis. CONCLUSIONS: An extensive arterial clot can be the initial presentation in COVID-19 patients and can be treated promptly with anticoagulation. Early introduction of prophylactic anticoagulation is necessary to prevent clot formation. REFERENCE #1:.Thromboinflammation and the hypercoagulability of COVID-19. Connors JM, Levy JH J Thromb Haemost.2020 Jul;18(7):1559-1561. REFERENCE #2: Coagulation disorders in coronavirus infected patients: COVID-19, SARS-CoV-1, MERS-CoV, and lessonsfrom the past.Giannis D, Ziogas IA, Gianni P J Clin Virol. 2020 Jun;127():104362. REFERENCE #3: Smith S A, Mutch N J, Baskar D, Rohloff P, Docampo R, Morrissey J H. Polyphosphate modulates bloodcoagulation and fibrinolysis. Proc Natl Acad Sci U S A. 2006;103(04):903–908. DISCLOSURES: No relevant relationships by Sumit Gami, source=Web Response No relevant relationships by Subash Ghimire, source=Web Response No relevant relationships by Sushmita Khadka, source=Web Response No relevant relationships by Shobha Mandal, source=Web Response

Venous thrombosis, thromboembolism, biomarkers of inflammation, and coagulation in coronavirus disease 2019

ObjectiveCoronavirus disease 2019 (COVID-19) is associated with abnormal inflammatory and coagulation markers, potentially mediating thrombotic events. Our objective was to investigate the incidence, time course, laboratory features, and in-hospital outcomes of COVID-19 patients with suspected venous thromboembolism (VTE). MethodsA retrospective observational cohort study was conducted of patients hospitalized with COVID-19 who had undergone ultrasound imaging for suspected VTE from March 13 to May 18, 2020. The medical records of the included patients were reviewed for D-dimer, fibrinogen, prothrombin time, partial thromboplastin time, platelet count, C-reactive protein (CRP), and high-sensitivity troponin T at admission and at up to seven time points before and after ultrasound examination. The clinical outcomes included superficial venous thrombosis, deep vein thrombosis, pulmonary embolism, intubation, and death. Mixed effects logistic, linear, and Cox proportional hazards methods were used to evaluate the relationships between the laboratory markers and VTE and other in-hospital outcomes. ResultsOf 138 patients who had undergone imaging studies, 44 (31.9%) had evidence of VTE. On univariable analysis, an elevated admission CRP (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.01-1.09; P = .02; per 10-U increase in CRP), platelet count (OR, 1.48; 95% CI, 1.04-2.12; P = .03; per 1000-U increase in platelet count), and male sex (OR, 2.64; 95% CI, 1.19-5.84; P = .02), were associated with VTE. However only male sex remained significant on multivariable analysis (OR, 2.37; 95% CI, 1.01-5.56; P = .048). The independent predictors of death included older age (hazard ratio [HR], 1.04; 95% CI, 1.00-1.07; P = .04), active malignancy (HR, 4.39; 95% CI, 1.39-13.91; P = .01), elevated admission D-dimer (HR, 1.016; 95% CI, 1.003-1.029; P = .02), and evidence of disseminated intravascular coagulation (HR, 4.81; 95% CI, 1.76-13.10; P = .002). ConclusionsMale sex, elevated CRP, and elevated platelet count at admission were associated with VTE on univariable analysis. However, only male sex remained significant on multivariable analysis. Older age, active malignancy, disseminated intravascular coagulation, and elevated D-dimer at admission were independently associated with death for patients hospitalized with COVID-19.

Evidence-based for venous thromboembolism prevention to Perioperative patients in Orthopedic

Objective To integrate best evidence of venous thromboembolism (VTE) prevention into practice, improve nurses′ compliance, and reduce incidence of VTE in orthopaedic department. Methods Guided by standard procedure in JBI-Paces program, collected best evidence from online databases and set standards. Collected data through field observation, interviews and review of nursing records. A total of 167 patients and 36 nurses we recruited in study and audited twice. We judged result by knowledge level of nurses and nurses′ compliance with evidence and incidence rate of VTE. Results In baseline review, three criteria of poor compliance, the correct situation of daily inspection of VTE risk Wear gradient pressure stockings correctly for VTE high-risk patients, Intermittent pneumatic compression device (IPCD) used twice a day for 30 minutes each time, were significantly improved after application of evidence, increased from 47.22% (17/36) ,36.11% (13/36) ,36.11% (13/36) to 86.11% (31/36) , 86.11% (31/36) , 91.67 (33/36) respectively (χ2=12.25, 18.94, 24.08, all P < 0.05); The incidence of VTE decreased from 2.7% to 0 (P=0.195); correct rate of VTE risk assessment, awareness rate of health education among implementation rate of physical preventive measures and qualified rate of VTE-related knowledge and skills among nurses increased from 82.43% (61/74) ,74.32% (55/74) ,83.78% (62/74) ,77.03% (57/74) to 97.85% (91/93) ,91.40% (85/93) ,97.85% (91/93) ,96.77% (90/93) respectively (χ2= 8.86-15.24, all P < 0.01) . Conclusion The integration of best evidence standardize nurses′ behaviors, reduce incidence rate of VTE, improve quality of clinical care and promote satisfaction of patients continuously. Key words: Venous thromboembolism prevention; Evidence-based nursing; Best practice

Design and Implementation of a Comprehensive Surveillance System for Venous Thromboembolism in a Defined Region Using Electronic and Manual Approaches.

Systematic surveillance for venous thromboembolism (VTE) in the United States has been recommended by several organizations. Despite adoption of electronic medical records (EMRs) by most health care providers and facilities, however, systematic surveillance for VTE is not available. This article develops a comprehensive, population-based surveillance strategy for VTE in a defined geographical region. The primary surveillance strategy combined computerized searches of the EMR with a manual review of imaging data at the Duke University Health System in Durham County, North Carolina, United States. Different strategies of searching the EMR were explored. Consolidation of results with autopsy reports (nonsearchable in the EMR) and with results from the Durham Veterans' Administration Medical Center was performed to provide a comprehensive report of new VTE from the defined region over a 2-year timeframe. Monthly searches of the primary EMR missed a significant number of patients with new VTE who were identified by a separate manual search of radiology records, apparently related to delays in data entry and coding into the EMR. Comprehensive searches incorporating a location-restricted strategy were incomplete due to the assigned residence reflecting the current address and not the address at the time of event. The most comprehensive strategy omitted the geographic restriction step and identified all patients with VTE followed by manual review of individual records to remove incorrect entries (e.g., outside the surveillance time period or geographic location; no evidence for VTE). Consolidation of results from the EMR searches with results from autopsy reports and the separate facility identified additional patients not diagnosed within the Duke system. We identified several challenges with implementing a comprehensive VTE surveillance program that could limit accuracy of the results. Improved electronic strategies are needed to cross-reference patients across multiple health systems and to minimize the need for manual review and confirmation of results.

Cancer associated thrombosis in patients taking direct oral anticoagulants (DOACs): Retrospective review of a single institutional series.

e14080 Background: Venous thromboembolism (VTE) is a common and often serious complication for patients with malignancy. Even though low molecular weight heparin (LMWH) is recommended as first line therapy for initial and long term anticoagulation, patient choice may demand oral anticoagulants. This retrospective review illustrates the repeated observation of recurrent thromboembolic disease in patients taking the new class of oral anticoagulant, DOAC. Methods: The pharmacy database at our institution was searched to identify oncology patients who had received a prescription for a DOAC (rivaroxaban or apixiban). Sixtyfive patients were identified and case records were then examined for evidence of venous thromboembolism. Results: Five seperate episodes of recurrent venous thromboembolism were identified in four patients in our cohort., one patient having two seperate episodes of pulmonary embolus. All were on recommended therapeutic doses of DOAC at the time of thromboembolic event. Two patients experienced proven pulmonary embolus on CT pulmonary angiography (1 twice), one lower limb deep vein thrombosis and one upper limb deep vein thrombosis. Conclusions: This retrosepctive review reinforces the clinical guidelines stated by the Cochrane review and ASCO that LMWH should always be first line for the initial and continuation treatment of a VTE. The guidelines did not focus on the suboptimal anticoagulation aspect of the newer oral anticoagulants but more on the safety issues. Research has been mainly focused on comparing LMWH with unfractionated heparin (UFH) or oral warfarin. Comparisons between DOAC versus Warfarin as an oral form of therapy have also been made. In the available published literature, there is a paucity of research comparing DOACs to LMWH. We have identified four patients out of sixtyfive treated with therapeutic doses of DOAC who developed subsequent thromboembolism. This is additional supportive evidence that newer oral anticoagulant agents may not be efficacious in malignancy driven VTE and that LMWH should remain the standard of care. Patients specifically requesting DOAC for cancer associated VTE should be made aware of this data.

Tranexamic Acid for Treatment of Residual Subdural Hematoma After Bedside Twist-Drill Evacuation

Management of nonemergent, nonacute subdural hematomas (SDHs) ranges from observation to burr-hole evacuation or craniotomy, but recurrence rates are high. We evaluated the safety and efficacy of tranexamic acid (TXA) for the treatment of residual SDHs after bedside twist-drill evacuation. We performed a retrospective analysis of a prospectively maintained database from November 2013 to November 2014 for all patients who underwent placement of a bedside subdural evacuating port system (SEPS) followed by treatment with oral TXA (650 mg daily). All demographics, evidence of venous thromboembolism, and volumes of pertinent computed tomography were obtained. Twenty subdural hematomas in 14 patients met the inclusion criteria for this study. Most SDHs were mixed density. Mean SDH volume on presentation was 145.96 ± 40.22 cm(3) with a mean midline shift of 9.44 ± 4.84 mm. Mean volumes decreased to 80.00 ± 31.96 cm(3) and midline shift improved to 4.44 ± 3.29 mm after SEPS placement (P < 0.0001 and P= 0.0046). All patients were placed on TXA after their procedure. Mean follow-up with computed tomography was 92.1 ± 27.5 days, and mean SDH volume at last follow-up was 7.41 ± 15.54 cm(3) with a mean midline shift of 0.19 ± 0.69 mm (P < 0.0001 and P= 0.0002). Percent volume reduction was significantly higher after TXA than after SEPS (91.31% vs. 40.74%; P < 0.0001). No increase or delayed recurrence of the SDH was noted during TXA treatment. All but 1 clinical presenting symptom improved at follow-up. No venous thromboembolisms were noted among the patients. In our pilot study, chronic SDH volumes were reduced by 40.74% after SEPS drainage. The residual volume was reduced by an additional 91.31% during oral TXA treatment. No patients developed delayed recurrence or expansion of their SDHs. Further prospective studies are needed to evaluate the role of TXA for adjunctive treatment of chronic SDHs.

Patterns of Failure of a Standardized Perioperative Venous Thromboembolism Prophylaxis Protocol

Venous thromboembolism (VTE) is a leading contributor to morbidity after operations. We previously implemented a standardized VTE risk assessment, based on the Caprini score, along with risk-stratified prophylaxis. This system reduced the odds ratio of a VTE event from 3.02 to 0.75. We investigated patterns of failure to determine characteristics of patients in whom VTE develops despite the protocol. We reviewed all nontrauma general surgery patients with evidence of VTE after the inception of a VTE risk assessment and prophylaxis program. Characteristics were recorded, including demographics, diagnoses, operations, risk profile, prophylaxis prescribed, and regimen compliance. Twenty-seven patients failed the protocol and manifested VTE, representing an overall VTE rate of 0.3%. Of these patients, 63% had emergency operations and 52% underwent multiple operations, compared with 13% and 2.0% of the nontrauma general surgery population in whom VTE did not develop, respectively (p < 0.001). Of patients with VTE, 52% had pre-existing or postoperative infections, 22% had malignancies, but only 15% had missed 1 or more doses of pharmacologic prophylaxis during hospitalization. Five VTEs manifested after discharge; one of those patients was prescribed extended prophylaxis beyond hospitalization, and an extended course was not provided to 3 who were eligible. One patient had underestimation of the Caprini score due to lack of awareness of a family history of VTE. Emergency and multiple operations seem to confer dramatic hazards for VTE, despite standard prophylaxis. These factors are not currently captured in the Caprini model, but might be significant modifiers of risk that should prompt reassessment, perhaps with a weighted numeric value along with enhanced prophylaxis. It is encouraging that most patients received appropriate prophylaxis in compliance with the protocol.

Venous Thromboembolism Prophylaxis in Orthopaedic Trauma Patients: A Survey of OTA Member Practice Patterns and OTA Expert Panel Recommendations.

First, to provide the readership with a summation of the current practice patterns of North American orthopaedic surgeons for venous thromboembolism prophylaxis after musculoskeletal trauma. Second, to establish a set of guidelines and recommendations based on the most current and best available evidence for venous thromboembolism (VTE) prophylaxis after musculoskeletal trauma. A 24 item questionnaire titled "OTA VTE Prophylaxis Survey" was sent to active members of the Orthopaedic Trauma Association. PubMed and OVID/MEDLINE were used to search the current published literature regarding VTE prophylaxis in trauma patients using the following search terms: deep venous thrombosis, DVT, pulmonary embolism, PE, venous thromboembolism, VTE, prophylaxis, trauma, fracture, pneumatic compression device, PCD, sequential compression device, SCD, screening, ultrasound, duplex, ultrasonography, DUS, venography, magnetic resonance venography, MRV, inferior vena cava, IVC, filter, and IVCF. Each recommendation was graded using articles that were considered by the subcommittee as "the best available evidence" using the grading system adopted and endorsed by the American Academy of Orthopedic Surgeons' Evidenced Based Quality and Value committee. Overall, 185 of 1545 members completed the online survey. The range and variety of prophylaxis and screening methods used among orthopaedic trauma surgeons in North America is large, with a number of agents or methods for which no literature exists to support their use in musculoskeletal trauma. A set of recommendations and guidelines were constructed based on the results of the literature analysis and graded according to guidelines mentioned above. Due to the wide variability in practice patterns, poor scientific support for various therapeutic regimens and important medical-legal implications highlighted by the survey, a standardized set of guidelines and recommendations for VTE prophylaxis after musculoskeletal trauma will be critical in helping to improve patient care and minimize surgeons' exposure to potentially litigious activity. Therapeutic Level V. See Instructions for Authors for a complete description of levels of evidence.

Impact of thrombophilic genes mutations on thrombosis risk in Egyptian nonmetastatic cancer patients.

Venous thromboembolism (VTE) is a common complication in cancer patients. Several genetic risk factors related to thrombophilia are known; however, their contributions to thrombotic tendency in cancer patients have conflicting results. We aimed to determine the prevalence of factor V Leiden (FVL), prothrombin (PTH) G20210A and methylene tetrahydrofolate reductase (MTHFR) C677T gene polymorphisms in Egyptian nonmetastatic cancer patients and their influence on thrombosis risk in those patients. Factor V Leiden, PTH G20210A and MTHFR C677T polymorphisms were detected in 40 cancer patients with VTE (group 1) and 40 cancer patients with no evidence of VTE (group 2) by PCR-based DNA analysis. Factor V and MTHFR mutations were higher in group 1 than in group 2 (factor V heterozygous mutation: 20 vs. 7.5%, homozygous mutation: 10 vs. 2.5%; MTHFR heterozygous mutation: 40 vs. 25%, homozygous mutation 5 vs. 0%, respectively) (P = 0.03). Mortality rate was higher in group 1 (75%) than in group 2 (25%; P < 0.001). No difference was found between those groups regarding PTH mutation (P = 1). Mortality rate was higher in the presence of homozygous and heterozygous factor V mutation (100 and 82%, respectively) compared to the wild type (41%) (P = 0.0006). Having any of the three studied gene mutations worsened the overall survival (P = 0.0003). Cox regression proved that both thrombosis and presence of factor V mutation are independent factors affecting survival in cancer patients (P < 0.001 and P = 0.01, respectively). In conclusion, there is an association between factor V and MTHFR mutations and risk of VTE in Egyptian cancer patients. Thrombosis and presence of factor V mutation are independent factors that influence survival in those patients.

A Randomized Study on 1-Week Versus 4-Week Prophylaxis for Venous Thromboembolism After Laparoscopic Surgery for Colorectal Cancer

To compare the efficacy and safety of antithrombotic prophylaxis given for 1 week or 4 weeks in patients undergoing laparoscopic surgery for colorectal cancer. Extending antithrombotic prophylaxis beyond 1 week reduces the incidence of venous thromboembolism (VTE) after open abdominal surgery for cancer. In consecutive patients who underwent laparoscopic surgery for colorectal cancer, complete compression ultrasonography of the lower limbs was performed after 8 ± 2 days of antithrombotic prophylaxis. Patients with no evidence of VTE were randomized to short (heparin withdrawal) or to extended (heparin continued for 3 additional weeks) prophylaxis. Complete compression ultrasonography was repeated at day 28 ± 2 after surgery by investigators blinded to treatment allocation. The primary outcome of the study was the composite of symptomatic and ultrasonography-detected VTE at day 28 ± 2 after surgery. Overall, 301 patients were evaluated for inclusion in the study and 225 were randomized. VTE occurred in 11 of 113 patients randomized to short (9.7%) and in none of the 112 patients randomized to extended heparin prophylaxis (P = 0.001). The incidence of VTE at 3 months was 9.7% and 0.9% in patients randomized to short or to extended heparin prophylaxis, respectively (relative risk reduction: 91%, 95% confidence interval: 30%-99%; P = 0.005). The rate of bleeding was similar in the 2 treatment groups. Two patients died during the study period, 1 in each treatment group. After laparoscopic surgery for colorectal cancer, extended antithrombotic prophylaxis is safe and reduces the risk for VTE as compared with 1-week prophylaxis (NCT01589146).

High prevalence of protein C, protein S, antithrombin deficiency, and Factor V Leiden mutation as a cause of hereditary thrombophilia in patients of venous thromboembolism and cerebrovascular accident.

Objectives: To determine the frequency of Protein C, Protein S (PC & PS), antithrombin deficiency (AT III) and Factor V Leiden mutation (FVL) as a cause of thrombophilia in the patients with venous thromboembolism (VTE) and cerebrovascular accident (CVA). Methods: It was an observational study conducted at Department of Haematology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, Pakistan. All patients referred for thrombophilia screening from July 2009 to June 2012 were screened. Patients with evidence of VTE or CVA were screened for PC & PS, AT III deficiency, and FVL. Results: Total 404 patients of age between 1-71 years mean 33 ± 14 with male to female ratio of 2.4:1 had evidence of thrombophilia. Two hundred eighteen (54%) patients presented with CVA, 116 (29%) with deep vein thrombosis (DVT), 42 (10.5%) with pulmonary embolism (PE), and 28 (7.5%) with portal or mesenteric vein thrombosis (PV). Protein C & S deficiency was detected in 35/404 (8.7%), ATIII in 9/404 (2%), and FVL in 25/173 patients (14.5%). The findings were suggestive of a significant association of FVL mutation for developing DVT (OR=11.0, 95% C I 4.6-26.3), CVA (OR=5.7, 95% C I 2.1-15.1), and PV (OR=5.4, 95% C I 1.3-21.9). PC & PS deficiency was a significant risk factor for developing PE (OR=3, 95% C I 0.8-11.4). Conclusion: FVL mutation and Protein C & S are the leading causes of thrombophilia with strong association of Factor V Leiden mutation as risk for developing DVT.

Cost of venous thromboembolism in hospitalized medically ill patients

The results of a study to estimate the economic costs of venous thromboembolism (VTE) in hospitalized nonsurgical patients during initial admissions and subsequent to hospital discharge are presented. Using a database linking admission records from more than 150 U.S. hospitals to health insurance claims, 49,948 patients 40 years of age or older who were hospitalized at least once during a 6-year period for diagnoses other than VTE or traumatic injury and who met other inclusion criteria were identified. Costs were tallied from the index admission to postdischarge day 180 for patients with and patients without evidence of VTE. Ordinary least-squares regression was used to estimate the independent relationship between VTE and total health care costs, controlling for differences in patient characteristics. Two hundred forty-two patients (0.5%) had VTE during the index admission, 317 (0.6%) had VTE after the index admission discharge; in total, 559 (1.1%) had VTE through postdischarge day 180. Among the 242 patients with VTE during their index admission, the adjusted mean total health care costs over 180 days were $17,848 higher than among those without VTE ($47,416 versus $29,568, p < 0.001); for the 317 patients with postdischarge VTE, the adjusted mean total 180-day costs were $51,863 higher than for those without postdischarge VTE ($74,136 versus $22,273, p < 0.001). Among medically ill patients admitted to the hospital, health care costs were significantly higher among those who developed VTE during hospitalization or after discharge compared with those who did not develop VTE.

Effectiveness of MR angiography for the primary diagnosis of acute pulmonary embolism: clinical outcomes at 3 months and 1 year.

To determine the effectiveness of MR angiography for pulmonary embolism (MRA-PE) in symptomatic patients. We retrospectively reviewed all patients whom were evaluated for possible pulmonary embolism (PE) using MRA-PE. A 3-month and 1-year from MRA-PE electronic medical record (EMR) review was performed. Evidence for venous thromboembolism (VTE) (or death from PE) within the year of follow-up was the outcome surrogate for this study. There were 190 MRA-PE exams performed with 97.4% (185/190) of diagnostic quality. There were 148 patients (120 F: 28 M) that had both a diagnostic MRA-PE exam and 1 complete year of EMR follow-up. There were 167 patients (137 F: 30 M) with 3 months or greater follow-up. We found 83% (139/167) and 81% (120/148) MRA-PE exams negative for PE at 3 months and 1 year, respectively. Positive exams for PE were seen in 14% (23/167). During the 1-year follow-up period, five patients (false negative) were diagnosed with DVT (5/148 = 3.4 %), and one of these patients also experienced a non-life-threatening PE. The negative predictive value (NPV) for MRA-PE was 97% (92-99; 95% CI) at 3 months and 96% (90-98; 95% CI) with 1 year of follow-up. The NPV of MRA-PE, when used for the primary diagnosis of pulmonary embolism in symptomatic patients, were found to be similar to the published values for CTA-PE. In addition, the technical success rate and safety of MRA-PE were excellent.

Venous thromboembolism and coagulation activity in patients with immune thrombocytopenia treated with thrombopoietin receptor agonists

Venous thromboembolism and coagulation activity in patients with immune thrombocytopenia treated with thrombopoietin receptor agonists

Intravenous administration of auto serum-expanded autologous mesenchymal stem cells in stroke

Transplantation of human mesenchymal stem cells has been shown to reduce infarct size and improve functional outcome in animal models of stroke. Here, we report a study designed to assess feasibility and safety of transplantation of autologous human mesenchymal stem cells expanded in autologous human serum in stroke patients. We report an unblinded study on 12 patients with ischaemic grey matter, white matter and mixed lesions, in contrast to a prior study on autologous mesenchymal stem cells expanded in foetal calf serum that focused on grey matter lesions. Cells cultured in human serum expanded more rapidly than in foetal calf serum, reducing cell preparation time and risk of transmissible disorders such as bovine spongiform encephalomyelitis. Autologous mesenchymal stem cells were delivered intravenously 36-133 days post-stroke. All patients had magnetic resonance angiography to identify vascular lesions, and magnetic resonance imaging prior to cell infusion and at intervals up to 1 year after. Magnetic resonance perfusion-imaging and 3D-tractography were carried out in some patients. Neurological status was scored using the National Institutes of Health Stroke Scale and modified Rankin scores. We did not observe any central nervous system tumours, abnormal cell growths or neurological deterioration, and there was no evidence for venous thromboembolism, systemic malignancy or systemic infection in any of the patients following stem cell infusion. The median daily rate of National Institutes of Health Stroke Scale change was 0.36 during the first week post-infusion, compared with a median daily rate of change of 0.04 from the first day of testing to immediately before infusion. Daily rates of change in National Institutes of Health Stroke Scale scores during longer post-infusion intervals that more closely matched the interval between initial scoring and cell infusion also showed an increase following cell infusion. Mean lesion volume as assessed by magnetic resonance imaging was reduced by >20% at 1 week post-cell infusion. While we would emphasize that the current study was unblinded, did not assess overall function or relative functional importance of different types of deficits, and does not exclude placebo effects or a contribution of recovery as a result of the natural history of stroke, our observations provide evidence supporting the feasibility and safety of delivery of a relatively large dose of autologous mesenchymal human stem cells, cultured in autologous human serum, into human subjects with stroke and support the need for additional blinded, placebo-controlled studies on autologous mesenchymal human stem cell infusion in stroke.

Risk Factors of Venous Thromboembolism in Indian Patients with Pelvic-Acetabular Trauma

To determine risk factors of venous thromboembolism (VTE) in Indian patients undergoing surgery for pelvic-acetabular fractures. 48 men and 8 women aged 17 to 61 (mean, 36) years who underwent open reduction and internal fixation for pelvic-acetabular fractures were evaluated for VTE in the postoperative period. Pulmonary angiography and indirect computed tomographic venography were used in the hospital, whereas colour Doppler ultrasonography was used in an outpatient setting until postoperative week 6. Patients with evidence of VTE were treated according to the American College of Chest Physician guidelines. Correlations between VTE and putative variable were assessed, and risk factors determined. 16 patients developed VTE. Six patients with proximal DVT had associated pulmonary embolism (PE). There were 12 cases of proximal deep vein thrombosis (DVT), 2 cases of distal DVT, and 10 cases of PE. The rate of VTE was significantly higher in patients who had predominantly posterior injury (as opposed to anterior injury) [13/27 vs. 3/29, p=0.003], who were operated on in the lateral position (as opposed to the supine position) [13/30 vs. 3/26, p=0.016], or via the Kocher-Langenbeck or combined approach (as opposed to others) [13/30 vs. 3/26, p=0.016]. Patients were more likely to develop VTE when they had predominantly posterior injuries (7.8 fold) or were operated on in a lateral position (2.96 fold) or via the Kocher-Langenbeck approach (2.27 fold). Pelvic-acetabular trauma is a significant risk factor for VTE, even in Indians. Patients who have posterior injuries or are operated on in the lateral position, or via the Kocher-Langenbeck approach have a significantly higher risk of VTE.

Use of Retrievable Filters in Alternative Common Iliac Vein Location in High-risk Surgical Patients

Purpose To evaluate the use of retrievable filters placed in bilateral common iliac veins in high-risk surgical patients. Materials and Methods During the 4-year study period, 10 patients received bilateral common iliac vein placement of retrievable filters for pulmonary embolism (PE) prophylaxis. These patients were at risk for venous thromboembolism (VTE) but had no evidence of VTE at the time of filter placement. In nine patients undergoing bariatric surgery, placement of a filter in the inferior vena cava (IVC) was impossible because of megacava (defined as caval diameter ≥3.0 cm). In one patient who had planned dissection of an extensive retroperitoneal tumor, there was concern that IVC location of the filter would be prone to complications secondary to intraoperative manipulation. Filter placement and retrieval were evaluated. All patients were followed clinically until 4–6 weeks after filter retrieval. Results There were 20 filters placed in 10 attempts, 18 (nine patients) through the right internal jugular vein and 2 (one patient) through bilateral femoral veins. The mean (± standard deviation) dwell time of the filters was 40 days ± 10 (range 30–71 days). All filters were successfully removed. There were no procedural complications. No clinically evident PE was noted. Conclusions Use of retrievable filters in the bilateral common iliac veins was found to be feasible and effective in preventing PE in patients with contraindications to filter placement in the IVC.

High prevalence of nonalcoholic fatty liver in patients with idiopathic venous thromboembolism

to assess the prevalence of nonalcoholic fatty liver disease (NAFLD) in patients with idiopathic venous thromboembolism (VTE). in a case-control study, after excluding subjects with well-consolidated risk factors for VTE, idiopathic VTE was documented in 138 consecutive patients who were referred to our department. Two hundred and seventy-six healthy sex/age/body-mass-index-matched subjects, without any clinical/instrumental evidence of VTE, served as controls. All underwent a clinical/laboratory/ultrasound assessment for the presence of metabolic syndrome and NAFLD. NAFLD was detected in 112/138 cases (81%) and in 84/276 controls (30%) [risk ratio: 2.7, 95% confidence interval (CI): 2.2-3.2, P < 0.0001]. Metabolic syndrome and smoking habit were more prevalent in patients with idiopathic VTE. The high prevalence of NAFLD in VTE was also confirmed after adjustment for inherited thrombophilia. NAFLD was clearly predicted by VTE (odds ratio: 1.8, 95% CI: 1.2-2.7, P < 0.0001). NAFLD was independently associated with idiopathic VTE.

The 19-bp deletion of dihydrofolate reductase (DHFR), methylenetetrahydrofolate reductase (MTHFR) C677T, Factor V Leiden, prothrombin G20210A polymorphisms in cancer patients with and without thrombosis

Venous thromboembolism (VTE) is a common complication in cancer patients. Several genetic risk factors related to thrombophilia are known; however, their contributions to thrombotic tendency in cancer patients have conflicting results. In the present study, we have focused on the prevalence of methylenetetrahydrofolate reductase (MTHFR) C677T, dihydrofolate reductase (DHFR) 19-bp deletion within intron 1, factor V Leiden (FVL), and prothrombin (PT) G20210A polymorphisms in cancer patients with and without VTE. The study consisted of 63 cancer patients with VTE (group 1) and 124 cancer patients who had no evidence of VTE (group 2). Four gene polymorphisms were determined by the method of polymerase-chain-reaction-based DNA analysis. The prevalence of DHFR 19-bp deletion and MTHFR C677T polymorphisms was similar in two groups (p > 0.05). The frequency of FVL was significantly higher in group1 compared with group 2 (31.7% vs. 1.6%, p < 0.0001), but PT G20210A polymorphism was not associated with VTE. Cancer patients with thrombosis should be evaluated for FVL, but routine screening for PT G20210A, MTHFR C677T and DHFR 19-bp deletion polymorphisms is not suggested.

Calciphylaxis: An important imitator of cutaneous vasculitis

Case Report A 42-year-old man was transferred to our institution for management of severe ulcerations of the lower extremities thought to be secondary to vasculitis. Three months previously, the patient was hit on the left shin by a soccer ball. The next day, his left pretibial region became erythematous and swollen. He was given cephalexin for presumed cellulitis, and the erythema improved but the swelling did not. Within a few days, the erythema returned and the swelling extended to his calf. Small, tight bullae formed over the affected skin. His right leg also began to swell and blister. The patient developed generalized edema and decreased urine output. He was admitted to an outside hospital. The patient had hypertension and a baseline creatinine level of 2 mg/dl. Medications included amlodipine, furosemide, and acetaminophen/propoxyphene napsylate. There were no known drug allergies. Social and family histories were noncontributory. Upon admission, the patient was afebrile and vital signs were normal except for a blood pressure of 150/90 mm Hg. The examination was remarkable for erythema of the lower extremities with 3 pitting edema and mild flexion contractures of the knees. The skin below the knees was covered with scattered bullae, indurated violaceous patches, and ulcers. Initial laboratory results are shown in Table 1. A portable chest radiograph showed cardiomegaly with clear lung fields. Renal ultrasound revealed a right renal cyst, increased cortical echogenicity, and diminished renal cortices. Cephalexin was continued, and dialysis was initiated. Results of blood and urine cultures were negative. Cultures of the wounds grew mixed bowel and skin flora. Erythrocyte sedimentation rate was 85 mm/hour. Hepatitis B and C serologies, antinuclear antibody, antineutrophil cytoplasmic antibodies, and cryoglobulins were negative. Serum protein electrophoresis was normal. Intact parathyroid hormone (PTH) was increased at 196.5 pg/ml (normal range 10–55 pg/ml). There was no evidence of venous thromboembolism on duplex ultrasonography of the lower extremities or by a ventilation/perfusion scan. Transthoracic echocardiogram showed no evidence of endocarditis, atrial myxoma, or atheroembolic disease. Despite ciprofloxacin and ceftazidime, whirlpool treatments, and wound debridement, numerous ulcers with black eschar and indurated, erythematous margins developed below the knees. New violaceous and indurated lesions progressed proximally to involve the thighs followed by the lower abdomen. Punch biopsy samples of the left and right thigh were reported as necrotizing vasculitis. Treatment with methylprednisolone 60 mg intravenously every 6 hours was begun. The histopathologic findings, however, also included focal fat necrosis and a patent blood vessel with mural calcification, features suggesting calciphylaxis. A repeat punch biopsy sample of the thigh obtained 1 week later for immunofluorescent studies showed vascular and perivascular fibrin deposits that were suggestive of atrophie blanche from stasis dermatitis or livedo vasculitis. Mycophenolate mofetil was initiated and subsequently discontinued days later, when blood cultures grew Pseudomonas and Enterobacter. Computed tomography of the chest, abdomen, and pelvis revealed no masses or lymphadenopathy. Rheumatoid factor, anticardiolipin antibodies, lupus anticoagulant, and anti–double-stranded DNA antibody were repeatedly negative. Serum C3 and C4 were normal. Three months after the initial admission the patient was transferred to our institution for further treatment. He was stable and afebrile but in severe pain. The physical examination revealed extensive skin involvement (Figure 1). A necrotic lesion was present over the left lower abdomen Supported by the South Jersey Lupus Foundation. Dana Jacobs-Kosmin, MD: Albert Einstein Medical Center, Philadelphia, Pennsylvania; Raphael J. DeHoratius, MD: Thomas Jefferson University, Philadelphia, Pennsylvania. Address correspondence to Dana Jacobs-Kosmin, MD, Einstein Arthritis Center, 5501 Old York Road, Korman 103, Philadelphia, PA 19141. E-mail: jacobkd@einstein.edu. Submitted for publication May 10, 2006; accepted in revised form August 31, 2006. Arthritis & Rheumatism (Arthritis Care & Research) Vol. 57, No. 3, April 15, 2007, pp 533–537 DOI 10.1002/art.22616 © 2007, American College of Rheumatology