Background The total annual number of VTE events and related deaths in the US is unknown, largely... more Background The total annual number of VTE events and related deaths in the US is unknown, largely because the complete spectrum of disease (including asymptomatic events and sudden deaths) occurring in the community is under-recognized. Objective To estimate the total annual number of non-fatal and fatal deep vein thrombosis (DVT) and pulmonary embolism (PE) events (incident and recurrent) in the US. Methods We developed an incidence-based model that included both hospital- and community-acquired VTE events as well as death from recognized and unrecognized VTE. We estimated the annual number of community-acquired events using the average age-, sex-, and event-specific incidence rates in Olmsted County, MN (1966–1990) and Y2000 US census data. We estimated the annual number of hospital-acquired events using patient age and Y2002 International Classification of Disease (ICD-9) discharge diagnosis codes for major surgery types or acute medical illnesses within the Healthcare Utilizatio...
Introduction Hereditary antithrombin (AT) deficiency is an autosomal dominant thrombophilia. It i... more Introduction Hereditary antithrombin (AT) deficiency is an autosomal dominant thrombophilia. It is classified into type 1 (quantitative) or type 2 (qualitative) deficiency based on the AT antigen and activity levels (Haemophilia 2008:14; 1229). The goal of this study was to correlate clinical phenotype with AT molecular defects. Methods After IRB approval, patients with a diagnosis of hereditary AT deficiency established at the Mayo Clinic, Rochester, were identified from the clinical database (1997-2012). AT activity was assayed by a chromogenic Factor Xa assay and AT antigen level was assayed by latex immunoassay. Peripheral blood leukocyte genomic DNA was extracted using standard methods. PCR-amplification and ABI BigDye Terminator cycle sequencing kit was performed for all SERPINC1 exons, intronic splicing regions and the 3’UTR. SERPINC1 sequence was analyzed using Mutation Surveyor software (SoftGenetics). Clinical data were obtained from patient interview and medical record re...
1159 Background. Heparin induced thrombocytopenia (HIT) is an immune disorder where platelets are... more 1159 Background. Heparin induced thrombocytopenia (HIT) is an immune disorder where platelets are activated by antibodies to a complex of platelet factor 4 antigen and heparin (PF4/H), leading to thrombocytopenia (HIT) and, potentially, thrombosis (HITT). Documentation of anti-PF4/H antibodies in addition to the appropriate clinical findings is essential for making a diagnosis of HIT. In the post-cardiac bypass surgery setting, however, the frequency of elevated anti-PF4/H antibodies is high, whereas the frequency of clinical HIT or HITT is relatively uncommon. Several studies have shown that the presence of anti-PF4/H antibodies may be associated with an increased frequency of adverse outcomes, even in the absence of clinical HIT. The primary objective of this study was to determine the relationship between a positive PF4/H antibody in the postoperative setting with adverse thromboembolic events occurring up to 3 months after cardiac surgery. Methods. Patients undergoing cardiac su...
Active cancer is an independent VTE risk factor (overall 6- to 9-fold increased risk) and account... more Active cancer is an independent VTE risk factor (overall 6- to 9-fold increased risk) and accounts for almost 20% of all VTE in the community, but which cancer patients are at risk for VTE is largely unknown. Reportedly, VTE risk varies by tumor site, and cancer of the ovary, pancreas, colon, stomach, lung, prostate, and kidney convey particularly high VTE risk. Objective: To estimate VTE risk by tumor site. Methods: We enumerated observed cancers by tumor site for Olmsted County, MN active cancer patients with incident VTE over the seven-year period, 1991–1997 (n=152). We used 1991–1997 State Surveillance, Epidemiology, and End Results (SEER) data for Iowa to estimate the expected age-specific prevalence of cancer by tumor site in Olmsted County. VTE risk ratios (RR) for each tumor site were estimated by dividing the observed number of cancers by the expected number (calculated as the product of the SEER prevalence and the number of incident VTE cases in the age stratum). Results: ...
4201 Background: Hereditary AT deficiency is classified as type 1 (quantitative) or type 2 (quali... more 4201 Background: Hereditary AT deficiency is classified as type 1 (quantitative) or type 2 (qualitative). Type 2 deficiency can be further subdivided into type 2a (reactive center loop [RCL]), type 2b (heparin binding domain), and type 2c (pleiotropic) based on functional and molecular AT analysis. Patients with heterozygous type 2b AT deficiency are thought to be at a lower risk for venous thromboembolism (VTE). Objectives: 1) To estimate the frequency of type 2 hereditary AT deficiency. 2) To utilize molecular analysis to accurately sub type patients with type 2 defects. 3) To correlate thrombotic and obstetric complications with AT deficiency sub types. Methods: Apparently unrelated Mayo Clinic AT-deficient patients (n=20) were categorized as type 1 or 2 based on plasma AT activity and antigen, or by molecular analysis for previously reported type 2a-c mutations. Demographic and clinical characteristics were abstracted from patient medical records. The SERPINC1 putative promoter ...
Age is the dominant risk factor for most chronic human diseases; yet the mechanisms by which agin... more Age is the dominant risk factor for most chronic human diseases; yet the mechanisms by which aging confers this risk are largely unknown. Recently, the age-related acquisition of somatic mutations in regenerating hematopoietic stem cell populations was associated with both hematologic cancer incidence and coronary heart disease prevalence. Somatic mutations with leukemogenic potential may confer selective cellular advantages leading to clonal expansion, a phenomenon termed 'Clonal Hematopoiesis of Indeterminate Potential' (CHIP). Simultaneous germline and somatic whole genome sequence analysis now provides the opportunity to identify root causes of CHIP. Here, we analyze high-coverage whole genome sequences from 97,691 participants of diverse ancestries in the NHLBI TOPMed program and identify 4,229 individuals with CHIP. We identify associations with blood cell, lipid, and inflammatory traits specific to different CHIP genes. Association of a genome-wide set of germline gen...
SummaryWe performed a double-blind, randomized clinical trial to compare the efficacy and safety ... more SummaryWe performed a double-blind, randomized clinical trial to compare the efficacy and safety of three different subcutaneous (SC) low molecular weight heparin doses (ardeparin sodium 25,35, or 50 anti-XaU/kg twice daily [BID]) to adjusted-dose warfarin (international normalized ratio [INR] = 2.0 to 3.0), as venous thromboembolism prophylaxis after total knee replacement surgery. The primary endpoint was total venous thromboembolism prevalence, defined as deep vein thrombosis discovered at postoperative venography of the operated leg, or symptomatic, objectively-documented pulmonary embolism. Of 860 patients randomized, 680 (79%) had an evaluable venogram or pulmonary embolism. The total venous thromboembolism prevalence was significantly greater among patients prophylaxed with warfarin compared to ardeparin 50 BID (38% vs 27%, p = 0.019); the prevalence among ardeparin 25 BID (37%) and 35 BID (28%) patients was similar to warfarin and ardeparin 50 BID patients, respectively. Ove...
Nursing home (NH) residency is an independent risk factor for venous thromboembolism (VTE), but t... more Nursing home (NH) residency is an independent risk factor for venous thromboembolism (VTE), but the VTE burden within the NH population is uncertain. This study estimates VTE incidence and VTE-associated mortality among NH residents. We identified all NH residents in any NH in Olmsted County, Minnesota, United States, 1 October 1998 to 31 December 2005 and all first lifetime VTE among county residents to estimate VTE incidence while resident of local NHs (NHVTE), using Centers for Medicare and Medicaid Services Minimum Data Set and Rochester Epidemiology Project resources. We tested associations between NHVTE and age, sex and time since each NH admission using Poisson modelling. Additionally, we tested incident NHVTE as a potential predictor of survival using Cox proportional hazards, adjusting for age, sex and NH residency. Between 1 October 1998 and 31 December 2005, 3,465 Olmsted County residents with ≥1 admission to a local NH, contributed 4,762 NH stays. Of the 3,465 NH residen...
Coronary embolism is the underlying cause of 3% of acute coronary syndromes but is often not cons... more Coronary embolism is the underlying cause of 3% of acute coronary syndromes but is often not considered in the differential of acute coronary syndromes. It should be suspected in the case of high thrombus burden despite a relatively normal underlying vessel or recurrent coronary thrombus. Coronary embolism may be direct (from the aortic valve or left atrial appendage), paroxysmal (from the venous circulation through a patent foramen ovale), or iatrogenic (following cardiac intervention). Investigations include transesophageal echocardiography to assess the left atrial appendage and atrial septum and continuous electrocardiographic monitoring to assess for paroxysmal atrial fibrillation. The authors review the historic and contemporary published data about this important cause of acute coronary syndromes. The authors propose an investigation and management strategy for work-up and anticoagulation strategy for patients with suspected coronary embolism.
Platelet transmission electron microscopy (PTEM) is considered the gold standard test for assessi... more Platelet transmission electron microscopy (PTEM) is considered the gold standard test for assessing distinct ultrastructural abnormalities in inherited platelet disorders (IPDs). Nevertheless, PTEM remains mainly a research tool due to the lack of standardized procedures, a validated dense granule (DG) count reference range, and standardized image interpretation criteria. The aim of this study was to standardize and validate PTEM as a clinical laboratory test. Based on previously established methods, we optimized and standardized preanalytical, analytical, and postanalytical procedures for both whole mount (WM) and thin section (TS) PTEM. Mean number of DG/platelet (plt), percentage of plts without DG, platelet count (PC), mean platelet volume (MPV), immature platelet fraction (IPF), and plt light transmission aggregometry analyses were measured on blood samples from 113 healthy donors. Quantile regression was used to estimate the reference range for DG/plt, and linear regression wa...
International journal of environmental research and public health, Jan 15, 2017
Certain diseases can occur with and without a trigger. We use Venous Thromboembolism (VTE) as our... more Certain diseases can occur with and without a trigger. We use Venous Thromboembolism (VTE) as our example to identify genetic interaction with pregnancy in women with VTE during pre- or postpartum. Pregnancy is one of the major risk factors for VTE as it accounts for 10% of maternal deaths. We performed a whole genome association analysis using the Cox Proportional Hazard (CoxPH) model adjusted for covariates to identify genetic variants associated with the time-to-event of VTE related to pre- or postpartum during the childbearing age of 18-45 years using a case-only design in a cohort of women with VTE. Women with a VTE event after 45 years of age were censored and contributed only follow-up time. We identified two intragenic single nucleotide polymorphisms (SNPs) at genome-wide significance in the PURB gene located on chromosome 7, and two additional intragenic SNPs, one in the LINGO2 gene on chromosome 9 and one in RDXP2 on chromosome X. We showed that the time-to-event model is ...
Observational studies have shown an association between obesity and venous thromboembolism (VTE) ... more Observational studies have shown an association between obesity and venous thromboembolism (VTE) but it is not known if observed associations are causal, due to reverse causation or confounding bias. We conducted a Mendelian Randomization study of body mass index (BMI) and VTE. We identified 95 single nucleotide polymorphisms (SNPs) that have been previously associated with BMI and assessed the association between genetically predicted high BMI and VTE leveraging data from a previously conducted GWAS within the INVENT consortium comprising a total of 7507 VTE cases and 52,632 controls of European ancestry. Five BMI SNPs were associated with VTE at PÂ <Â 0.05, with the strongest association seen for the FTO SNP rs1558902 (OR 1.07, 95% CI 1.02-1.12, PÂ =Â 0.005). In addition, we observed a significant association between genetically predicted BMI and VTE (ORÂ =Â 1.59, 95% CI 1.30-1.93 per standard deviation increase in BMI, PÂ =Â 5.8Â Ă—Â 10(-6)). Our study provides evidence for a causal rela...
Seminars in Thrombosis and Hemostasis, Sep 1, 2002
Identification of risk factors for incident venous thromboembolism and predictors of recurrent ve... more Identification of risk factors for incident venous thromboembolism and predictors of recurrent venous thromboembolism and appropriate antithrombotic prophylaxis and therapy are vital to improve survival after pulmonary embolism and prevent complications such as venous stasis syndrome after deep-vein thrombosis. Risk stratification is increasingly important; future prophylaxis and treatment strategies should be targeted to the patients who will derive the greatest benefit. For established antithrombotic agents, the most appropriate dose, dosing schedule, and duration of prophylaxis and therapy are being refined. In addition, new antithrombotic agents such as the oral direct thrombin inhibitors are being identified and developed. The management of acute arterial thrombosis (for example, acute coronary syndromes) is an important and relatively new indication for antithrombotic agents such as the low-molecular-weight heparins and the platelet glycoprotein IIb/IIIa antagonists.
Data Revues 00123692 V133i6 S0012369208601233, Aug 8, 2011
This article discusses the prevention of venous thromboembolism (VTE) and is part of the Antithro... more This article discusses the prevention of venous thromboembolism (VTE) and is part of the Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Grade 1 recommendations are strong and indicate that the benefits do or do not outweigh risks, burden, and costs. Grade 2 suggestions imply that individual patient values may lead to different choices (for a full discussion of the grading, see the &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;Grades of Recommendation&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; chapter by Guyatt et al). Among the key recommendations in this chapter are the following: we recommend that every hospital develop a formal strategy that addresses the prevention of VTE (Grade 1A). We recommend against the use of aspirin alone as thromboprophylaxis for any patient group (Grade 1A), and we recommend that mechanical methods of thromboprophylaxis be used primarily for patients at high bleeding risk (Grade 1A) or possibly as an adjunct to anticoagulant thromboprophylaxis (Grade 2A). For patients undergoing major general surgery, we recommend thromboprophylaxis with a low-molecular-weight heparin (LMWH), low-dose unfractionated heparin (LDUH), or fondaparinux (each Grade 1A). We recommend routine thromboprophylaxis for all patients undergoing major gynecologic surgery or major, open urologic procedures (Grade 1A for both groups), with LMWH, LDUH, fondaparinux, or intermittent pneumatic compression (IPC). For patients undergoing elective hip or knee arthroplasty, we recommend one of the following three anticoagulant agents: LMWH, fondaparinux, or a vitamin K antagonist (VKA); international normalized ratio (INR) target, 2.5; range, 2.0 to 3.0 (each Grade 1A). For patients undergoing hip fracture surgery (HFS), we recommend the routine use of fondaparinux (Grade 1A), LMWH (Grade 1B), a VKA (target INR, 2.5; range, 2.0 to 3.0) [Grade 1B], or LDUH (Grade 1B). We recommend that patients undergoing hip or knee arthroplasty or HFS receive thromboprophylaxis for a minimum of 10 days (Grade 1A); for hip arthroplasty and HFS, we recommend continuing thromboprophylaxis &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 10 days and up to 35 days (Grade 1A). We recommend that all major trauma and all spinal cord injury (SCI) patients receive thromboprophylaxis (Grade 1A). In patients admitted to hospital with an acute medical illness, we recommend thromboprophylaxis with LMWH, LDUH, or fondaparinux (each Grade 1A). We recommend that, on admission to the ICU, all patients be assessed for their risk of VTE, and that most receive thromboprophylaxis (Grade 1A).
Journal of Thrombosis and Thrombolysis, Sep 1, 2001
Common indications for chronic anticoagulation include mechanical prosthetic heart valve, non-rhe... more Common indications for chronic anticoagulation include mechanical prosthetic heart valve, non-rheumatic atrial fibrillation, and venous thromboembolism. Perioperative management of the chronically anticoagulated patient is a complex medical problem, and includes the following issues: urgency of surgery, risk of thromboembolism in the absence of anticoagulation, bleeding risk, consequences of bleeding, ability to control bleeding physically, and duration of bleeding risk after the procedure. Most patients can be managed safely by stopping oral anticoagulants 4-5 days before surgery and restarting anticoagulation after the procedure at the patient's usual daily dose. In general, dental procedures and cataract extraction can be performed without interrupting anticoagulation. Most other procedures can be safely performed with an INR < or = 1.4. For patients with double-wing prosthetic valves (e.g., St. Jude, Carbomedics) in the aortic position, uncomplicated atrial fibrillation, or a remote (>3 months) history of venous thromboembolism, oral anticoagulants can be stopped 4-5 days before surgery and restarted at the usual daily dose immediately after surgery. For other patients at higher risk of thrombosis, "bridging therapy" with outpatient low molecular weight heparin is safe and effective. For urgent procedures, a small dose of oral vitamin K usually will reduce the INR within 24-36 hours to a level sufficient for surgery and avoids exposure to transfused blood products.
Background The total annual number of VTE events and related deaths in the US is unknown, largely... more Background The total annual number of VTE events and related deaths in the US is unknown, largely because the complete spectrum of disease (including asymptomatic events and sudden deaths) occurring in the community is under-recognized. Objective To estimate the total annual number of non-fatal and fatal deep vein thrombosis (DVT) and pulmonary embolism (PE) events (incident and recurrent) in the US. Methods We developed an incidence-based model that included both hospital- and community-acquired VTE events as well as death from recognized and unrecognized VTE. We estimated the annual number of community-acquired events using the average age-, sex-, and event-specific incidence rates in Olmsted County, MN (1966–1990) and Y2000 US census data. We estimated the annual number of hospital-acquired events using patient age and Y2002 International Classification of Disease (ICD-9) discharge diagnosis codes for major surgery types or acute medical illnesses within the Healthcare Utilizatio...
Introduction Hereditary antithrombin (AT) deficiency is an autosomal dominant thrombophilia. It i... more Introduction Hereditary antithrombin (AT) deficiency is an autosomal dominant thrombophilia. It is classified into type 1 (quantitative) or type 2 (qualitative) deficiency based on the AT antigen and activity levels (Haemophilia 2008:14; 1229). The goal of this study was to correlate clinical phenotype with AT molecular defects. Methods After IRB approval, patients with a diagnosis of hereditary AT deficiency established at the Mayo Clinic, Rochester, were identified from the clinical database (1997-2012). AT activity was assayed by a chromogenic Factor Xa assay and AT antigen level was assayed by latex immunoassay. Peripheral blood leukocyte genomic DNA was extracted using standard methods. PCR-amplification and ABI BigDye Terminator cycle sequencing kit was performed for all SERPINC1 exons, intronic splicing regions and the 3’UTR. SERPINC1 sequence was analyzed using Mutation Surveyor software (SoftGenetics). Clinical data were obtained from patient interview and medical record re...
1159 Background. Heparin induced thrombocytopenia (HIT) is an immune disorder where platelets are... more 1159 Background. Heparin induced thrombocytopenia (HIT) is an immune disorder where platelets are activated by antibodies to a complex of platelet factor 4 antigen and heparin (PF4/H), leading to thrombocytopenia (HIT) and, potentially, thrombosis (HITT). Documentation of anti-PF4/H antibodies in addition to the appropriate clinical findings is essential for making a diagnosis of HIT. In the post-cardiac bypass surgery setting, however, the frequency of elevated anti-PF4/H antibodies is high, whereas the frequency of clinical HIT or HITT is relatively uncommon. Several studies have shown that the presence of anti-PF4/H antibodies may be associated with an increased frequency of adverse outcomes, even in the absence of clinical HIT. The primary objective of this study was to determine the relationship between a positive PF4/H antibody in the postoperative setting with adverse thromboembolic events occurring up to 3 months after cardiac surgery. Methods. Patients undergoing cardiac su...
Active cancer is an independent VTE risk factor (overall 6- to 9-fold increased risk) and account... more Active cancer is an independent VTE risk factor (overall 6- to 9-fold increased risk) and accounts for almost 20% of all VTE in the community, but which cancer patients are at risk for VTE is largely unknown. Reportedly, VTE risk varies by tumor site, and cancer of the ovary, pancreas, colon, stomach, lung, prostate, and kidney convey particularly high VTE risk. Objective: To estimate VTE risk by tumor site. Methods: We enumerated observed cancers by tumor site for Olmsted County, MN active cancer patients with incident VTE over the seven-year period, 1991–1997 (n=152). We used 1991–1997 State Surveillance, Epidemiology, and End Results (SEER) data for Iowa to estimate the expected age-specific prevalence of cancer by tumor site in Olmsted County. VTE risk ratios (RR) for each tumor site were estimated by dividing the observed number of cancers by the expected number (calculated as the product of the SEER prevalence and the number of incident VTE cases in the age stratum). Results: ...
4201 Background: Hereditary AT deficiency is classified as type 1 (quantitative) or type 2 (quali... more 4201 Background: Hereditary AT deficiency is classified as type 1 (quantitative) or type 2 (qualitative). Type 2 deficiency can be further subdivided into type 2a (reactive center loop [RCL]), type 2b (heparin binding domain), and type 2c (pleiotropic) based on functional and molecular AT analysis. Patients with heterozygous type 2b AT deficiency are thought to be at a lower risk for venous thromboembolism (VTE). Objectives: 1) To estimate the frequency of type 2 hereditary AT deficiency. 2) To utilize molecular analysis to accurately sub type patients with type 2 defects. 3) To correlate thrombotic and obstetric complications with AT deficiency sub types. Methods: Apparently unrelated Mayo Clinic AT-deficient patients (n=20) were categorized as type 1 or 2 based on plasma AT activity and antigen, or by molecular analysis for previously reported type 2a-c mutations. Demographic and clinical characteristics were abstracted from patient medical records. The SERPINC1 putative promoter ...
Age is the dominant risk factor for most chronic human diseases; yet the mechanisms by which agin... more Age is the dominant risk factor for most chronic human diseases; yet the mechanisms by which aging confers this risk are largely unknown. Recently, the age-related acquisition of somatic mutations in regenerating hematopoietic stem cell populations was associated with both hematologic cancer incidence and coronary heart disease prevalence. Somatic mutations with leukemogenic potential may confer selective cellular advantages leading to clonal expansion, a phenomenon termed 'Clonal Hematopoiesis of Indeterminate Potential' (CHIP). Simultaneous germline and somatic whole genome sequence analysis now provides the opportunity to identify root causes of CHIP. Here, we analyze high-coverage whole genome sequences from 97,691 participants of diverse ancestries in the NHLBI TOPMed program and identify 4,229 individuals with CHIP. We identify associations with blood cell, lipid, and inflammatory traits specific to different CHIP genes. Association of a genome-wide set of germline gen...
SummaryWe performed a double-blind, randomized clinical trial to compare the efficacy and safety ... more SummaryWe performed a double-blind, randomized clinical trial to compare the efficacy and safety of three different subcutaneous (SC) low molecular weight heparin doses (ardeparin sodium 25,35, or 50 anti-XaU/kg twice daily [BID]) to adjusted-dose warfarin (international normalized ratio [INR] = 2.0 to 3.0), as venous thromboembolism prophylaxis after total knee replacement surgery. The primary endpoint was total venous thromboembolism prevalence, defined as deep vein thrombosis discovered at postoperative venography of the operated leg, or symptomatic, objectively-documented pulmonary embolism. Of 860 patients randomized, 680 (79%) had an evaluable venogram or pulmonary embolism. The total venous thromboembolism prevalence was significantly greater among patients prophylaxed with warfarin compared to ardeparin 50 BID (38% vs 27%, p = 0.019); the prevalence among ardeparin 25 BID (37%) and 35 BID (28%) patients was similar to warfarin and ardeparin 50 BID patients, respectively. Ove...
Nursing home (NH) residency is an independent risk factor for venous thromboembolism (VTE), but t... more Nursing home (NH) residency is an independent risk factor for venous thromboembolism (VTE), but the VTE burden within the NH population is uncertain. This study estimates VTE incidence and VTE-associated mortality among NH residents. We identified all NH residents in any NH in Olmsted County, Minnesota, United States, 1 October 1998 to 31 December 2005 and all first lifetime VTE among county residents to estimate VTE incidence while resident of local NHs (NHVTE), using Centers for Medicare and Medicaid Services Minimum Data Set and Rochester Epidemiology Project resources. We tested associations between NHVTE and age, sex and time since each NH admission using Poisson modelling. Additionally, we tested incident NHVTE as a potential predictor of survival using Cox proportional hazards, adjusting for age, sex and NH residency. Between 1 October 1998 and 31 December 2005, 3,465 Olmsted County residents with ≥1 admission to a local NH, contributed 4,762 NH stays. Of the 3,465 NH residen...
Coronary embolism is the underlying cause of 3% of acute coronary syndromes but is often not cons... more Coronary embolism is the underlying cause of 3% of acute coronary syndromes but is often not considered in the differential of acute coronary syndromes. It should be suspected in the case of high thrombus burden despite a relatively normal underlying vessel or recurrent coronary thrombus. Coronary embolism may be direct (from the aortic valve or left atrial appendage), paroxysmal (from the venous circulation through a patent foramen ovale), or iatrogenic (following cardiac intervention). Investigations include transesophageal echocardiography to assess the left atrial appendage and atrial septum and continuous electrocardiographic monitoring to assess for paroxysmal atrial fibrillation. The authors review the historic and contemporary published data about this important cause of acute coronary syndromes. The authors propose an investigation and management strategy for work-up and anticoagulation strategy for patients with suspected coronary embolism.
Platelet transmission electron microscopy (PTEM) is considered the gold standard test for assessi... more Platelet transmission electron microscopy (PTEM) is considered the gold standard test for assessing distinct ultrastructural abnormalities in inherited platelet disorders (IPDs). Nevertheless, PTEM remains mainly a research tool due to the lack of standardized procedures, a validated dense granule (DG) count reference range, and standardized image interpretation criteria. The aim of this study was to standardize and validate PTEM as a clinical laboratory test. Based on previously established methods, we optimized and standardized preanalytical, analytical, and postanalytical procedures for both whole mount (WM) and thin section (TS) PTEM. Mean number of DG/platelet (plt), percentage of plts without DG, platelet count (PC), mean platelet volume (MPV), immature platelet fraction (IPF), and plt light transmission aggregometry analyses were measured on blood samples from 113 healthy donors. Quantile regression was used to estimate the reference range for DG/plt, and linear regression wa...
International journal of environmental research and public health, Jan 15, 2017
Certain diseases can occur with and without a trigger. We use Venous Thromboembolism (VTE) as our... more Certain diseases can occur with and without a trigger. We use Venous Thromboembolism (VTE) as our example to identify genetic interaction with pregnancy in women with VTE during pre- or postpartum. Pregnancy is one of the major risk factors for VTE as it accounts for 10% of maternal deaths. We performed a whole genome association analysis using the Cox Proportional Hazard (CoxPH) model adjusted for covariates to identify genetic variants associated with the time-to-event of VTE related to pre- or postpartum during the childbearing age of 18-45 years using a case-only design in a cohort of women with VTE. Women with a VTE event after 45 years of age were censored and contributed only follow-up time. We identified two intragenic single nucleotide polymorphisms (SNPs) at genome-wide significance in the PURB gene located on chromosome 7, and two additional intragenic SNPs, one in the LINGO2 gene on chromosome 9 and one in RDXP2 on chromosome X. We showed that the time-to-event model is ...
Observational studies have shown an association between obesity and venous thromboembolism (VTE) ... more Observational studies have shown an association between obesity and venous thromboembolism (VTE) but it is not known if observed associations are causal, due to reverse causation or confounding bias. We conducted a Mendelian Randomization study of body mass index (BMI) and VTE. We identified 95 single nucleotide polymorphisms (SNPs) that have been previously associated with BMI and assessed the association between genetically predicted high BMI and VTE leveraging data from a previously conducted GWAS within the INVENT consortium comprising a total of 7507 VTE cases and 52,632 controls of European ancestry. Five BMI SNPs were associated with VTE at PÂ <Â 0.05, with the strongest association seen for the FTO SNP rs1558902 (OR 1.07, 95% CI 1.02-1.12, PÂ =Â 0.005). In addition, we observed a significant association between genetically predicted BMI and VTE (ORÂ =Â 1.59, 95% CI 1.30-1.93 per standard deviation increase in BMI, PÂ =Â 5.8Â Ă—Â 10(-6)). Our study provides evidence for a causal rela...
Seminars in Thrombosis and Hemostasis, Sep 1, 2002
Identification of risk factors for incident venous thromboembolism and predictors of recurrent ve... more Identification of risk factors for incident venous thromboembolism and predictors of recurrent venous thromboembolism and appropriate antithrombotic prophylaxis and therapy are vital to improve survival after pulmonary embolism and prevent complications such as venous stasis syndrome after deep-vein thrombosis. Risk stratification is increasingly important; future prophylaxis and treatment strategies should be targeted to the patients who will derive the greatest benefit. For established antithrombotic agents, the most appropriate dose, dosing schedule, and duration of prophylaxis and therapy are being refined. In addition, new antithrombotic agents such as the oral direct thrombin inhibitors are being identified and developed. The management of acute arterial thrombosis (for example, acute coronary syndromes) is an important and relatively new indication for antithrombotic agents such as the low-molecular-weight heparins and the platelet glycoprotein IIb/IIIa antagonists.
Data Revues 00123692 V133i6 S0012369208601233, Aug 8, 2011
This article discusses the prevention of venous thromboembolism (VTE) and is part of the Antithro... more This article discusses the prevention of venous thromboembolism (VTE) and is part of the Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Grade 1 recommendations are strong and indicate that the benefits do or do not outweigh risks, burden, and costs. Grade 2 suggestions imply that individual patient values may lead to different choices (for a full discussion of the grading, see the &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;Grades of Recommendation&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; chapter by Guyatt et al). Among the key recommendations in this chapter are the following: we recommend that every hospital develop a formal strategy that addresses the prevention of VTE (Grade 1A). We recommend against the use of aspirin alone as thromboprophylaxis for any patient group (Grade 1A), and we recommend that mechanical methods of thromboprophylaxis be used primarily for patients at high bleeding risk (Grade 1A) or possibly as an adjunct to anticoagulant thromboprophylaxis (Grade 2A). For patients undergoing major general surgery, we recommend thromboprophylaxis with a low-molecular-weight heparin (LMWH), low-dose unfractionated heparin (LDUH), or fondaparinux (each Grade 1A). We recommend routine thromboprophylaxis for all patients undergoing major gynecologic surgery or major, open urologic procedures (Grade 1A for both groups), with LMWH, LDUH, fondaparinux, or intermittent pneumatic compression (IPC). For patients undergoing elective hip or knee arthroplasty, we recommend one of the following three anticoagulant agents: LMWH, fondaparinux, or a vitamin K antagonist (VKA); international normalized ratio (INR) target, 2.5; range, 2.0 to 3.0 (each Grade 1A). For patients undergoing hip fracture surgery (HFS), we recommend the routine use of fondaparinux (Grade 1A), LMWH (Grade 1B), a VKA (target INR, 2.5; range, 2.0 to 3.0) [Grade 1B], or LDUH (Grade 1B). We recommend that patients undergoing hip or knee arthroplasty or HFS receive thromboprophylaxis for a minimum of 10 days (Grade 1A); for hip arthroplasty and HFS, we recommend continuing thromboprophylaxis &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 10 days and up to 35 days (Grade 1A). We recommend that all major trauma and all spinal cord injury (SCI) patients receive thromboprophylaxis (Grade 1A). In patients admitted to hospital with an acute medical illness, we recommend thromboprophylaxis with LMWH, LDUH, or fondaparinux (each Grade 1A). We recommend that, on admission to the ICU, all patients be assessed for their risk of VTE, and that most receive thromboprophylaxis (Grade 1A).
Journal of Thrombosis and Thrombolysis, Sep 1, 2001
Common indications for chronic anticoagulation include mechanical prosthetic heart valve, non-rhe... more Common indications for chronic anticoagulation include mechanical prosthetic heart valve, non-rheumatic atrial fibrillation, and venous thromboembolism. Perioperative management of the chronically anticoagulated patient is a complex medical problem, and includes the following issues: urgency of surgery, risk of thromboembolism in the absence of anticoagulation, bleeding risk, consequences of bleeding, ability to control bleeding physically, and duration of bleeding risk after the procedure. Most patients can be managed safely by stopping oral anticoagulants 4-5 days before surgery and restarting anticoagulation after the procedure at the patient's usual daily dose. In general, dental procedures and cataract extraction can be performed without interrupting anticoagulation. Most other procedures can be safely performed with an INR < or = 1.4. For patients with double-wing prosthetic valves (e.g., St. Jude, Carbomedics) in the aortic position, uncomplicated atrial fibrillation, or a remote (>3 months) history of venous thromboembolism, oral anticoagulants can be stopped 4-5 days before surgery and restarted at the usual daily dose immediately after surgery. For other patients at higher risk of thrombosis, "bridging therapy" with outpatient low molecular weight heparin is safe and effective. For urgent procedures, a small dose of oral vitamin K usually will reduce the INR within 24-36 hours to a level sufficient for surgery and avoids exposure to transfused blood products.
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