History Of Thromboembolic Disease Research Articles

Two Doses of Tranexamic Acid Reduce Blood Transfusion in Complex Spine Surgery: A Prospective Randomized Study.

Prospective, double-blinded, randomized controlled study. To determine whether the use of 2 doses of tranexamic acid (TXA) can reduce perioperative blood loss and blood transfusions in low-risk adult patients undergoing complex laminectomy. Complex laminectomy (multilevel laminectomy or laminectomy and instrumentation) is a procedure with a medium risk of blood loss, which may require allogeneic blood transfusion. Previous studies of TXA showed its inconsistent effectiveness in reducing blood loss during spine surgery. The negative results may stem from ineffective use of a single dose of TXA during long and complex operations. 80 adult (18-65 yr old) patients in Siriraj Hospital, Mahidol University, Thailand were enrolled and allocated into 2 groups (40 patients in each group) by computer-generated randomization. Patients with history of thromboembolic diseases were excluded. Anesthesiologists in charge and patients were blinded. Group I received 0.9% NaCl (NSS) or placebo and group II received 2 doses (15 mg/kg) of TXA. The first dose was administered before anesthesia induction and the second dose, after 3 hours. The assessed outcomes were the amount of perioperative blood loss and the incidence of blood transfusions. 78 patients were analyzed (1 patient in each group was excluded) with 39 patients randomized to each group. There were no differences in patient demographics and pre and postoperative hematocrit levels. The total blood loss in the control group (NSS) was higher [900 (160, 4150) mL] than in the TXA group [600 (200, 4750) mL]. Patients in the control group received more crystalloid, colloid, and packed red blood cell transfusions. Within 24 hours, we observed a 64.6% reduction of blood transfusions (43.5% vs.15.4%, P = 0.006). No serious thromboembolic complications occurred. 2 effective doses (15 mg/kg) of TXA can reduce blood loss and transfusions in low-risk adults undergoing complex spine surgery. 1.

Chronic Thromboembolic Pulmonary Hypertension: the End Result of Pulmonary Embolism.

Chronic thromboembolic pulmonary hypertension (CTEPH) occurs when a pulmonary embolism fails to undergo complete thrombolysis leading to vascular occlusion and pulmonary hypertension. Despite the fact that CTEPH is a potential consequence of pulmonary embolism, diagnosis requires a high degree of vigilance as many patients will not have a history of thromboembolic disease. The ventilation perfusion scan is used to evaluate for the possibility of CTEPH although right heart catheterization and pulmonary artery angiogram are needed to confirm the diagnosis. Pulmonary thromboendarterectomy is the first-line treatment for patients who are surgical candidates. Recently, riociguat has been approved for patients with nonsurgical disease or residual pulmonary hypertension despite surgical intervention. This review describes the pathophysiology, risk factors, diagnosis, and management of CTEPH.

Impact of left ventricular late enhancement on pulmonary arterial hypertension in idiopathic dilated cardiomyopathy

Methods 71 consecutive patients (p) with DCM, left ventricular systolic dysfunction (LVEF<35%) and normal coronary angiography followed in an outpatient HF clinic, were prospectively enrolled in two institutions. All p had to be in stable clinical condition in the last month. Exclusion criteria were: contraindications for contrast-enhanced cardiac MR (ce-CMR), significant impairment of lung function by clinical criteria or spirometry and history of thromboembolic disease. All patients underwent ECG, echo, blood test and a ce-CMR study in a Philips Intera ® 1.5 T scanner, which included cine imaging, phase contrast in the main pulmonary artery and aorta and late enhancement (LE). Postprocessing was performed with QMASS 7.2 ® (Medis, The Netherlands). PVR was calculated following the equation: 19.38 -(4.62*Ln pulmonary artery average velocity) (0.08 x RVEF %)

Prospective study of catheter-related central vein thrombosis in home parenteral nutrition patients with benign disease using serial venous Doppler ultrasound

Catheter-related central vein thrombosis (CRVT) is a severe complication of home parenteral nutrition (HPN) that may be clinically manifest or subclinical. The aims of the study were to prospectively investigate the incidence of CRVT in patients on HPN with benign disease and determine the influence of different variables on this complication. A prospective, multicentre, observational study in the Home Artificial Nutrition-Chronic Intestinal Failure ESPEN group was performed. Patients with benign disease starting HPN or already on HPN after the insertion of a new catheter, were recruited and followed up with Color Doppler Duplex Sonography (CDDS) evaluations at baseline, 1 week, 3, 6 and 12 months after catheter insertion. Fisher's exact test was used to calculate the association of different variables (related to the patient, type of catheter, vascular access, insertion method, catheter care and anticoagulant treatment) with CRVT events. Sixty-two patients (31 males, 31 females) aged 50±19 (19-83) years were included and followed for a median 363 days, with an Inter Quartile Range of 180-365 days, and a total of 16,186 catheter-days. Six patients had previous CRVT and 16 had history of thromboembolic disease (pulmonary and mesenteric). Forty one patients were receiving anticoagulant treatment. Fifty two patients had tunneled catheters and 10 implanted ports. Two patients had symptomatic thrombosis at 3 and 12 months of follow-up (2 and 3 weeks after normal routine CDDS evaluation). The incidence of CRVT was 0.045/catheter/year. CRVT was not significantly associated with any of the variables analyzed. The incidence of CRVT in patients on HPN for benign disease followed by CDDS is low in the first year of catheterization. We did not observe any case of asymptomatic CRVT. Based on our data, CDDS seems to have low effectiveness as a screening tool for CRVT in asymptomatic patients on HPN with benign disease.

Pulmonary Thromboembolectomy in Chronic Thromboembolic Pulmonary Hypertension: A Case Report and Review of Literature

Chronic thromboembolic pulmonary hypertension (CTEPH) is an important cause of severe pulmonary hypertention (PH) resulting in significant morbidity and mortality. Chronic thromboembolic PH occurs when a pulmonary embolism fails to undergo complete thrombolysis leading to vascular occlusion and pulmonary hypertension. Despite the fact that CTEPH is a potential consequence of pulmonary embolus, diagnosis requires a high degree of vigilance as many patients will not have a history of thromboembolic disease. The ventilation perfusion scan is used to evaluate for the possibility of CTEPH although right heart catheterization and pulmonary artery (PA) angiogram are needed to confirm the diagnosis. Pulmonary thromboendarterectomy is the first-line treatment for patients who are surgical candidates. This case report and review describes the pathophysiology, risk factors, diagnosis, and management of CTEPH. As it is a potentially curable cause of PH, its accurate diagnosis is vital. The gold standard and effective treatment for CTEPH is pulmonary endarterectomy (PEA). Pulmonary endarterectomy is an uncommon procedure with less than 50 years of experience worldwide. Research on the development of new surgical approaches is essential. In the present case, a new successful surgical technique for PEA was introduced. Conclusion: The surgical procedure used on the present patient was a unique technique. We do not claim that our technique is better than the original San Diego technique, but it is suggested as a modification that may improve patient survival. However, this procedure has its own limitations and cannot be used for clots that are located distally. Therefore, further experience should be obtained in order to overcome the limitations and improve the applicability of the technique.

Strut Penetration: Local Complications, Breakthrough Pulmonary Embolism, and Retrieval Failure in Patients with Celect Vena Cava Filters

PurposeTo investigate strut penetration in patients with Celect filters, specifically local complications and association with breakthrough pulmonary embolism (PE) or retrieval failure. Materials and MethodsA retrospective single-center study was conducted to evaluate patients who received Celect filters between January 2007 and May 2013. A total of 595 filters were placed during the study period. Primary indications included thromboembolic disease (93%) and primary surgical prophylaxis (7%). Complications and retrieval data were assessed by computed tomography (CT) and electronic medical records. ResultsA total of 193 patients underwent follow-up abdominal CT at a mean follow-up interval of 176.2 days (range, 0–1,739 d). The rate of strut penetration more than 3 mm outside the caval wall was 28.5% (n = 55). One patient had CT evidence of clinically major strut penetration (1.8%) with strut compression of the right ureter causing hydronephrosis. Indwelling filter time longer than 100 days was associated with strut penetration (P < .001). Age, sex, and history of thromboembolic disease were not associated with strut penetration (P = .51, P = .81, and P = .89). Sixty-three patients presented for follow-up CT pulmonary angiography at a mean of 128.1 days (range, 1–895 d). The rate of breakthrough PE was 12.7%. The overall retrieval success rate was 96.7% (n = 150). Strut penetration was not associated with breakthrough PE or retrieval failure (P = .49 and P = .22). ConclusionsAlthough strut penetration is a common complication with Celect filters, there is no association with breakthrough PE or retrieval failure. CT evidence of local complications associated with strut penetration is rare.

Necrosis cutánea por warfarina

La necrosis cutánea por warfarina aparece entre 0.01-0.1% de los pacientes, afecta más a mujeres con obesidad y antecedentes de enfermedad tromboembólica luego del quinto día de su inicio. Se debe a un imbalance transitorio de los sistemas anticoagulante y procoagulante, caracterizado por flictenas hemorrágicas en zonas con tejido graso. Reportamos el caso de una necrosis cutánea por warfarina con un desenlace fatal

Thrombotic thrombocytopenic purpura due to anti-ADAMTS13 antibodies in multiple myeloma

Thrombotic thrombocytopenic purpura (TTP) is a particularly serious form of thrombotic microangiopathy (TMA) due to the risk of multiple organ dysfunction. Several etiological factors such as infection, auto-immune disease, certain medications and cancers have been associated with TTP. A 74-year-old hypertensive woman with a history of thromboembolic disease was hospitalized for acute kidney injury (AKI) associated with pneumonia. Initial investigations were suggestive of Pneumocystis jirovecii infection and myeloma cast nephropathy. Several days later, the patient presented features of TTP. Von Willebrand factor-cleaving protease activity was less than 5% with a high level of IgG antibody directed against ADAMTS13. Treatment consisted of monthly 4-day cycles of dexamethasone and melphalan in combination with plasmapheresis and resulted in a favorable outcome. Three years after ceasing treatment, the patient presented no signs of hemolysis, but required chronic hemodialysis. The association of TMA, especially TTP, and multiple myeloma is exceptional. The authors report such a case that induced irreversible renal damage, but with stable clinical and laboratory parameters with a follow-up of 4 years.

Plasma Homocysteine in Patients with Retinal Vein Occlusion

To evaluate total plasma homocysteine (HCY) during fasting and post methionine load test (MLT), serum folate, serum vitamin B12, and methylenetetrahydrofolate reductase (MTHFR) mutation in patients with retinal vein occlusion (RVO) and to examine the association between these risk factors and 2 subtypes of RVO: central (CRVO) and branch (BRVO). This case-control study included 91 Italian patients presenting a first RVO and 71 healthy subjects, matched by age, without history of thromboembolic diseases, glaucoma, or malignancy. Homocysteine fasting and after MLT, serum folate level, serum vitamin B12 level, and other laboratory tests were assessed. Genetic analysis for the C677T MTHFR mutation was performed. Multivariate logistic regression analysis indicated that hypertension (odds ratio [OR] 2.63; 95% confidence interval [CI] 1.30-5.30; p = 0.007), higher values of fasting HCY (OR 1.16; 95% CI 1.01-1.33; p = 0.03), and low concentrations of vitamin B12 (OR 0.99; 95% CI 0.995-0.999; p = 0.01) were independently correlated with RVO. Moreover, the main determinants for CRVO risk were hypertension (OR 2.46; 95% CI 1.06-5.72; p = 0.04), high values of fasting HCY (OR 1.20; 95% CI 1.02-1.41; p = 0.03), and low concentrations of vitamin B12 (OR 0.99; 95% CI 0.994-0.999; p = 0.008), whereas for BRVO risk only hypertension was significant (OR 2.74; 95% CI 1.24-6.03; p = 0.01). Genotype distribution of the MTHFR C677T mutation did not reveal any significant difference between patients and controls. These results suggest that elevated fasting HCY levels, low vitamin B12 levels, and hypertension are associated with a risk of RVO, especially for CRVO. Moreover, our data suggest that only hypertension is associated with BRVO risk.

Anatomopathological Causes of Death in Patients with Advanced Cancer: Association with the Use of Anticoagulation and Antibiotics at the End of Life

Anatomopathological studies that described the immediate causes of death of patients with advanced cancer were first published approximately 20 years ago. Our objective was to analyze if causes of death changed with a wider use of broad spectrum antibiotics and prophylactic anticoagulation. We conducted a retrospective study of all patients with an advanced cancer hospitalized in the Division of Palliative Medicine at the University Hospital Geneva from 2004 to 2010 who had an autopsy. Two hundred forty patients were included (130 men, mean age: 74±13). Main causes of death discovered at the autopsy were pulmonary infection (n=131; 55%), advanced cancer (n=39; 16%), pulmonary infection together with pulmonary embolism (PE) (n=27; 12%), PE alone (n=22; 9%), cardiac complications (n=19; 5%) and others (n=2; 1%). In a logistic regression model, with adjusting for age, gender, main diagnosis, comorbidities, blood count, corticosteroids, and antibiotics, there were no independent factors associated with pulmonary infection at autopsy. In a similar model, with adjusting for age, gender, main diagnosis, comorbidities, and anticoagulation, the only independent factor associated with PE at autopsy was the history of thrombo-embolic disease and therapeutic anticoagulation. The results of this retrospective study demonstrate that causes of death did not change with the modification of our practice. The high rate of pulmonary infection and embolism in this population, including in patients who received broad spectrum and prophylactic anticoagulation should encourage us to pursue other prospective studies to actually demonstrate the benefit of these treatments in this population.

Phase I Study of Eltrombopag for Promoting Thrombopoiesis in Patients Undergoing Stem Cell Transplantation After Total Body Irradiation

AbstractAbstract 219 Purpose:Prolonged intervals of thrombocytopenia are common after stem cell transplantation, and platelet transfusions are the only temporary therapy before engraftment. Risk of thrombocytopenia is greater in patients receiving total body irradiation (TBI) in their conditioning regimen. Eltrombopag is a small-molecule, nonpeptide oral agent that functions as an agonist of the thrombopoietin receptor. It is approved by the FDA for the treatment of chronic idiopathic thrombocytopenic purpura and is being developed as a treatment for thrombocytopenia of other various etiologies. We report updated results of a Phase I clinical trial assessing the safety, pharmacokinetics (PK) and maximum tolerated dose (MTD) of once daily oral eltrombopag in patients undergoing stem cell transplantation with a conditioning regimen containing TBI ≥ 400 cGy. Methods:A Phase I dose-escalation clinical trial was conducted to evaluate the safety and PK of eltrombopag at 4 different dose levels: 75, 150, 225, and 300 mg given once daily for 27 days, starting 24–48 hours post stem cell transplantation to eligible patients ≥18 years old. Patients with various indications for stem cell transplantation, KPS ≥70%, and TBI ≥ 400 cGy were eligible. Patients receiving either an autologous (Auto) or allogeneic (Allo) stem cell transplantation from a sibling, related donor, or matched unrelated donor (MUD) were eligible. Stem cells from peripheral blood (PBSC) or bone marrow were permitted; however, cord blood stem cell transplantation was not permitted. Patients at risk of thromboembolism or with a history of thromboembolic disease in the preceding 6 months were excluded. PK sampling was obtained over a 24 hour period after the first dose of eltrombopag as well as during the second week of treatment (steady-state). Results:As of August 1 2012, a total of 19 subjects (7 AML, 4 lymphoma, 1 CML, 1 MDS, 1 myelofibrosis, 2 ALL, 1 APML, 1 Biphenotypic Leukemia and 1 CLL/SLL) were enrolled, and 15 completed protocol treatments. All 19 were PBSC transplants with 12 MUD, 6 Allo and 1 Auto. Three subjects were completed at each dose level up to 225 mg with six completing treatment at the highest dose of 300mg. Four subjects were replaced because drug compliance was less than 75%. To date, 11/19 are alive while 8/19 have died (3 related to graft vs. host disease (GVHD), 3 Infection-related and 2 related to disease progression (f/u interval: 5.7 – 30 months). No dose limiting toxicities (DLTs) have been observed. The most common adverse events (AEs) up to the 300 mg dose level were related to standard stem cell transplantation, which included low blood counts, fatigue, headache, diarrhea, nausea, peripheral edema, hypoalbuminemia, hyperglycemia, hypocalcemia, and hypomagnesemia. Possibly drug-related AEs were dry skin, rash, elevated creatinine, and hypokalemia; these were all grade 3 or less. There were 12 severe AEs observed in 8 subjects, which included infection (3/19), pulmonary embolism (PE) (1/19), acute renal failure (3/19), gastrointestinal (2/19), acute respiratory distress syndrome (1/19), pericarditis (1/19) and GvHD skin rash (1/19). Most SAEs were considered related to stem cell transplant, except one subject at 75 mg with PE possibly related to eltrombopag, but also possibly related to stem cell transplant and cancer diagnosis. The PE occurred 9 days after stopping eltrombopag at which time platelet count was 252K. Time to platelet engraftment and number of platelet transfusions were also documented for each enrolled patient. Median time to platelet engraftment for all subjects on this study was 16 days. PK data are summarized in Table 1 and Figure 1. A dose-dependent increase in plasma exposure of eltrombopag was observed; although some saturation of absorption is evident at the 300 mg dose level. (Figure 1). Conclusions:27-day once daily dosing of eltrombopag to enhance platelet recovery for post-transplant thrombocytopenia is well tolerated, with no DLTs observed up to the 300 mg dose level. Most AEs were transplant related. PK showed proportional plasma concentration up to 225 mg daily dosing, with some saturation of drug absorption above 225 mg. [Display omitted] [Display omitted] Disclosures:Liesveld:Eisai: Research Funding, Speakers Bureau; Bristol-Myers Squibb: Speakers Bureau; Ariad: Honoraria. Off Label Use: Eltrombopag not approved post-transplant. Dawson:GlaxoSmithKline: Employment.

Thromboembolic Events Following Surgery for Prostate Cancer

BackgroundProstate cancer (PCa) and surgery are both associated with increased risk of thromboembolic diseases (TED). ObjectiveWe assessed risk of TED among men undergoing different types of urologic surgery. Design, setting, and participantsUsing the Prostate Cancer Database Sweden (PCBaSe) Sweden, we identified all men (n=45 065) undergoing pelvic lymph node dissection (PLND), radical prostatectomy (RP) with or without PLND, orchiectomy due to PCa, or a transurethral resection of the prostate (TURP). We identified a comparison cohort from the population. Outcome measurements and statistical analysisMain outcomes were deep venous thrombosis (DVT) and pulmonary embolism (PE) as primary diagnoses in the National Patient Register or Cause of Death Register (2002–2010). We calculated hazard ratios (HR) and 95% confidence intervals (CI) using multivariable Cox proportional hazards models. Results and limitationsAll surgical procedures were associated with increased risk of TED; laparoscopic and open RP with a PLND were the most strongly associated with TED (HR for PE: 8.1 [95% CI, 2.9–23.0] and 7.8 [95% CI, 4.9–13], respectively). For surgery including a PLND, the risk increased during the second half of the first postoperative month. The HR for PE after TURP in men with PCa was 3.0 (95% CI, 1.8–5.1). Patients with a history of TED had a strongly increased risk of TED (HR for DVT: 4.5; 95% CI, 2.6–8.0). A limitation is lack of information on TED prophylaxis, but its use was standardized during the study period for RP and PLND. Other limitations are lack of information on extent of PLND and lifestyle factors. ConclusionsSurgeries for PCa, including TURP, are associated with hospitalization for TED. Patients with a history of TED and patients undergoing a PLND were at highest risk. The largest risk was observed from days 14 to 28 postoperatively. Thus, our results suggest that prophylactic measures may be beneficial during the first 4 wk in these patients.

Low Risk of Thromboembolic Complications With Tranexamic Acid After Primary Total Hip and Knee Arthroplasty

The use of antifibrinolytic medications in hip and knee arthroplasty reduces intraoperative blood loss and decreases transfusion rates postoperatively. Tranexamic acid (TXA) specifically has not been associated with increased thromboembolic (TE) complications, but concerns remain about the risk of symptomatic TE events, particularly when less aggressive chemical prophylaxis methods such as aspirin alone are chosen. We determined whether the rate of symptomatic TE events differed among patients given intraoperative TXA when three different postoperative prophylactic regimens were used after primary THA and TKA. We retrospectively reviewed 2046 patients who underwent primary THA or TKA and received TXA from 2007 to 2009. The three chemical regimens included aspirin alone, warfarin (target international normalized ratio, 1.8-2.2), and dalteparin. Primary outcome measures were venous TE events, including symptomatic deep vein thrombosis (DVT) and pulmonary embolism (PE), and arterioocclusive events, including myocardial infarction and cerebrovascular accident. Patients judged to be at high risk for TE due to recent cardiac stent placement or strong personal/family history of TE disease were excluded. For aspirin, warfarin, and dalteparin, the rates of symptomatic DVT (0.35%, 0.15%, and 0.52%, respectively) and nonfatal PE were similar (0.17%, 0.43%, and 0.26%, respectively). There were no fatal PE. Among the three groups, we found no difference in the rates of symptomatic DVT or PE with or without stratification by ASA score. A low complication rate was seen when using TXA as a blood conservation modality during primary THA and TKA with less aggressive thromboprophylactic regimens such as aspirin alone and dose-adjusted warfarin.

Phase I Study of Eltrombopag for Promoting Thrombopoiesis in Patients Undergoing Stem Cell Transplantation After Total Body Irradiation,

Abstract 3295▪▪This icon denotes a clinically relevant abstract Purpose:Prolonged intervals of thrombocytopenia are common after hematopoietic stem cell transplantation (HSCT), and platelet transfusions are the only effective therapy. Risk of thrombocytopenia is greater in patients (pts) receiving total body irradiation (TBI) in their conditioning regimen. Eltrombopag (ePag) is a small-molecule, nonpeptide oral agent that functions as an agonist of the thrombopoietin receptor. It is approved by FDA for the treatment of chronic ITP and is being developed as a treatment for thrombocytopenia of other various etiologies. We report results of an ongoing Phase I clinical trial assessing the safety, pharmacokinetics (PK) and maximum tolerated dose (MTD) of once daily oral ePag in pts undergoing HSCT with a conditioning regimen containing TBI ≥ 400 cGy. Methods:A Phase I dose-escalation clinical trial was conducted to evaluate the safety and PK of ePag at 4 different dose levels: 75, 150, 225, and 300 mg, once daily for 27 days, starting 24–48 hours post HSCT to eligible pts ≥18 yrs old. Pts with various indications for stem cell transplantation, KPS ≥70%, and TBI ≥ 400 cGy were eligible. Pts receiving either an autologous (Auto) or allogeneic (Allo) HSCT from a sibling, related donor, or matched unrelated donor (MUD) were eligible. Stem cells from peripheral blood (PBSC) or bone marrow were permitted; however, cord blood transplant was not permitted. Pts at risk of thromboembolism, or with a history of thromboembolic disease in the preceding 6 months, were excluded. PK sampling was obtained over a 24 h period after the first dose of ePag, as well as during the second week of treatment (steady-state). Results:As of July 1 2011, a total of 10 subjects (4 AML, 2 lymphoma, 1 CML, 1 MDS, 1 myelofibrosis, and 1 CLL/SLL) were enrolled, and 9 completed protocol treatments. All 9 were PBSC transplants with 6 MUD, 2 Allo and 1 Auto. Three subjects were completed at each dose level up to 225 mg. Enrollment is continuing at the 300 mg dose level. To date, 6/9 are alive while 3/9 died of non-relapse related causes (CMV pneumonitis and respiratory failure in 1, and steroid refractory GI GvHD in 2, f/u interval: 4.4 – 6.9 mo). No dose limiting toxicities (DLTs) have been observed. Most common adverse events up to 225 mg dose level were related to standard stem cell transplantation, which included low blood counts, fatigue, headache, diarrhea, nausea, peripheral edema, hypoalbuminemia, hyperglycemia, hypocalcemia, and hypomagnesemia. There were 9 SAEs observed in 5 pts, which included infection (3/9), pulmonary embolism (PE) (1/9), acute renal failure (2/9), gastrointestinal (2/9), and ARDS (1/9). Most SAEs were considered unrelated or unlikely related to ePag treatment except for the PE, which was considered possibly related to ePag but not considered a DLT. This subject had other risk factors for PE and the PE occurred 9 days after ePag had stopped at a platelet count of 252K. Time to platelet engraftment and number of platelet transfusions were documented for each enrolled pt. PK sampling demonstrated a dose dependent increase in plasma concentration of ePag (Figure 1). PK parameters for the 75, 150, and 225 mg dose levels are summarized in Table 1. [Display omitted] Table 1:Summary plasma PK parameters for 75, 150, and 225 mg dose levels from ELT112549aDose (mg)Ntmax (h)Cmax (μg/mL)AUC(0-τ) (μg.h/mL)Day 2Week 2Day 2Week 2Day 2Week 27534.07 (4.00, 6.00)4.00 (2.08, 6.33)4.57 (13)9.23 (37)48.9 (21)123 (24)15032.08 (2.00, 4.25)2.00 (1.00, 4.00)8.02 (35)15.6 (28)88.6 (18)253 (19)22534.00 (2.25, 4.32)2.00 (1.92, 4.08)18.7 (66)25.2 (65)190 (55)340 (76)aGeometric mean (CV%), except for tmax, median (minimum, maximum) Conclusions:27-day once daily dosing of ePag to enhance platelet recovery for post-transplant thrombocytopenia is well tolerated, with no DLTs observed up to the 225 mg dose level to date. Most AEs were transplant related. PK and the plasma exposure of ePag appears dose proportional over the studied dose range after single-dose and steady-state administration. Once-daily administration of up to 225 mg ePag for the transplant population receiving TBI ≥ 400 cGy as part of the conditioning regimen appears to be safe and well tolerated. Acknowledgment:The study is supported by Biomedical Advanced Research and Development Agency (BARDA), and by GlaxoSmithKline who also provided the study drug. Disclosures:Off Label Use: Promacta (eltrombopag) is an oral TPO Receptor agonist approved for the treatment of chronic ITP. The study being reported in this abstract is a phase I MTD study to evaluate eltrombopag for promoting thrombopoiesis in patients undergoing Stem Cell Transplantation after Total Body Irradiation. Dawson:GlaxoSmithKline: Employment.

Cardiac and thromboembolic complications and mortality in patients undergoing total hip and total knee arthroplasty

ObjectiveTo study 90-day complications following total hip arthroplasty (THA) or total knee arthroplasty (TKA).MethodIn a population-based cohort of all Olmsted County residents who underwent a THA or TKA (1994-2008), we...

Molecular Characterization of Factor V Leiden G1691A and Prothrombin G20210A Mutations in Saudi Newborns with Stroke

This study examined a possible association between the mutations related to Factor V Leiden and Factor II (prothrombin) and stroke in Saudi neonates. A multiplex PCR was established to detect Factor V Leiden G1691A and prothrombin G20210A mutations in 72 neonatal stroke subjects and 70 healthy adult controls with no family history of thromboembolic diseases. The frequency of the homozygous normal genotype (GG) of both genes was found to be significantly lower in the stroke subjects than in the controls (P < 0.0001). The stroke cases also had higher frequencies of the combined Factor II heterozygous mutant form (GA) and the homozygous normal Factor V (GG) (P < 0.0001) and of the combined heterozygous Factor V and the homozygous normal Factor II genotypes (GG) (P = 0.0) than controls. The study concluded that prothrombin and Factor V Leiden may be important risk factors for neonatal stroke in Saudi children.

Profilaxia para tromboembolia venosa em um hospital geral

To evaluate the use of venous thromboembolism (VTE) prophylaxis in a general hospital. A cross-sectional cohort study at the Hospital Nossa Senhora da Conceição, located in the city of Porto Alegre, Brazil, involving a random sample of patients admitted between October of 2008 and February of 2009. We included patients over 18 years of age and hospitalized for more than 48 h. The exclusion criteria were anticoagulant use, pregnancy, puerperium, and a history of thromboembolic disease. The adequacy of prophylaxis was evaluated in accordance with a protocol created by the Hospital and principally based on the American College of Chest Physicians guidelines, eighth edition. We included 262 patients. The mean age was 59.1 ± 16.6 years. The most common risk factors were immobilization (in 70.6%), infection (in 44.3%), cancer (in 27.5%), obesity (in 23.3%), and major surgery (in 14.1%). The risk of VTE was classified as high and moderate in 143 (54.6%) and 117 (44.7%) of the patients, respectively. Overall, 46.2% of the patients received adequate prophylaxis, 25% of those with > three risk factors for VTE and 18% of those with cancer, the differences between these last two groups and their counterparts (patients with < three risk factors and those without cancer) being statistically significant (p < 0.001 for both). Our data reveal that nearly all patients at our hospital were at risk for VTE, and that less than half received adequate VTE prophylaxis, which is in agreement with the literature. It is surprising that inadequate prophylaxis is more common in high-risk patients.

Thromboembolic Complications Following Spine Surgery Assessed with Spiral CT Scans

Spine surgery is associated with a significant risk of postoperative pulmonary embolism (PE) and/or deep vein thrombosis (DVT). The goal of this study was to determine which symptoms and risk factors were associated with spiral CT scans positive for PE and/or DVT in the postoperative spine surgery patient. We conducted a retrospective review of all spine patients who underwent a postoperative CT to rule out PE during the period of March 2004-February 2006. The type of surgical procedure, risk factors, symptoms prompting scan ordering, anticoagulation, and treatment were recorded. Logistic regression models were used to determine significant predictors of a positive CT in this patient population. Of the 3,331 patients that had spine surgery during the study period, 130 (3.9%) had a spiral CT scan to rule out PE and/or proximal DVT. Thirty-three of the 130 (25.4%) CT scans were positive for PE only, five (3.8%) for PE and DVT, and three (2.3%) for DVT only. Only 24.5% (32) patients had risk factors for thromboembolic disease, and of these, a history of PE and/or DVT was the only significant risk factor for a positive scan (p = 0.03). No presenting symptoms or demographic variables were noted to have a significant association with PE and/or DVT. The type of surgical procedure (i.e., anterior, posterior, and percutaneous) was not associated with an increased risk for PE and/or DVT. Patients who are undergoing spine surgery with a history of thromboembolic disease should be carefully monitored postoperatively and may benefit from more aggressive prophylaxis.

ADAMTS13 ACTIVITY and VON Willebrand FACTOR LEVELS IN PATIENTS with Livedoid VASCULOPATHY.

Abstract 5064 IntroductionLivedoid vasculopathy is a rare skin disease caused by the extensive formation of microthrombi in dermis vessels, which leads to infarction and ulceration of the epidermis. The pathogenesis of livedoid vasculopathy is unknown, and hypercoagulation states have been implicated. Moreover, success using anticoagulation was reported in some patients. We hypothesized that decreased levels of ADAMTS13 activity and Von Willebrand factor (vWF) levels could contribute to the pathogenesis of local thrombus formation in livedoid vasculopathy. ObjectiveHere we evaluated the levels of ADAMTS13 activity and vWF in patients with livedoid vasculopathy. Patients and methodsFourteen patients (93% female) with livedoid vasculopathy, median age of 41.5 years (22 - 48) were included in the study. All patients were evaluated for the presence of classical acquired and hereditary thrombophilia markers. In addition, vWF antigen levels (Elisa) and activity (collagen binding assays), as well as ADAMTS13 activity (evaluated by residual collagen binding) were evaluated. Resultsnine patients (64%) were carriers of the MTHFR C677T mutation (6 heterozygous and 3 homozygous); 1 patient was a carrier of factor V Leiden mutation, and 1 patient was a carrier of the FII G20210A mutation. None of the patients presented deficiency of antithrombin, protein C or S, and antiphospholipid antibodies were not identified in our study population. ADAMTS13 and VWF activities were normal in all patients. Median vWF antigen was 120.5U/dl (reference value of 40.0 - 232.0%), and vWF activity was 102.3% (reference value of 45.5 - 203.7%). ADAMTS13 activity was 138.9% (reference value of 56.0 - 227.2 %). Two patients had a history of thromboembolic diseases: one patient with 2 strokes and one patient with central retinal artery occlusion. ConclusionWe show here that ADAMTS13 activity and vWF levels are not altered in patients with livedoid vasculopathy. The MTHFR C677T mutation is frequent in patients with livedoid vasculopathy but quantification of homocysteine levels is necessary to consider any relationship with this disease. DisclosuresNo relevant conflicts of interest to declare.

Detection of Pulmonary Embolism in the Postoperative Orthopedic Patient Using Spiral CT Scans

Orthopedic surgery is associated with a significant risk of postoperative pulmonary embolism (PE) and/or deep vein thrombosis (DVT). This study was performed to compare the clinical presentations of a suspected versus a documented PE/DVT and to determine the actual incidence of PE/DVT in the post-operative orthopedic patient in whom CT was ordered. All 695 patients at our institution who had a postoperative spiral CT to rule out PE/DVT from March 2004 to February 2006 were evaluated and information regarding their surgical procedure, risk factors, presenting symptoms, location of PE/DVT, and anticoagulation were assessed. Statistical analysis was performed using an independent samples t test with a two-tailed p value to examine significant associations between the patient variables and CT scans positive for PE. Logistic regression models were used to determine which variables appeared to be significant predictors of a positive chest CT. Of 32,854 patients admitted for same day surgery across all services, 695 (2.1%) had a postoperative spiral CT based on specific clinical guidelines. The incidence of a positive scan was 27.8% (193/695). Of these, 155 (22.3%) scans were positive for PE only, 24 (3.5%) for PE and DVT, and 14 (2.0%) for DVT only. The most common presenting symptoms were tachycardia (56%, 393/695), low oxygen saturation (48%, 336/695), and shortness of breath (19.6%, 136/695). Symptoms significantly associated with DVT were syncope and chest pain. A past medical history of PE/DVT was the only significant predictor of a positive scan. Patients who have a history of thromboembolic disease should be carefully monitored in the postoperative setting.