Higher Baseline Hemoglobin and Splenectomy Are Risk Factors for Venous Thromboembolism in Adults with Sickle Cell Variant Genotypes

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3243-3243
Author(s):  
Rakhi P. Naik ◽  
Michael B. Streiff ◽  
Julie Nelson ◽  
Sophie Lanzkron
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Venous Thromboembolism ◽  
Venous Thrombosis ◽  
Sickle Cell ◽  
Research Funding ◽  
Hemoglobin Level ◽  
History Of ◽  
Cell Variant ◽  
Baseline Hemoglobin

Abstract Abstract 3243 Background: Sickle cell disease (SCD) is a hypercoagulable state, leading to increased rates of thrombotic complications such as stroke and venous thromboembolism (VTE). We have previously demonstrated an increased risk of non-catheter-related VTE among patients with sickle cell variant syndromes compared to those with sickle cell anemia (SS/Sβ0) genotypes. Variations in baseline laboratory values, including hemoglobin and hemolytic rate, have been shown to modify the risk of developing complications such as acute chest syndrome and retinopathy in SCD patients. In addition, splenectomy has been identified as a risk factor for VTE in patients with other hemoglobinopathies such as β-thalassemia intermedia. Therefore, we sought to determine the hematologic and clinical risk factors associated with VTE among our cohort of patients with SC and Sβ+thalassemia genotypes. Methods: We conducted a retrospective cohort study of all patients with hemoglobin SC or Sβ+thalassemia genotypes cared for at the Sickle Cell Center for Adults at Johns Hopkins between August 2008 and July 2012. Baseline hematologic parameters were recorded for all patients and were defined as steady-state outpatient laboratory values that were taken at least 1 month after a hospitalization and at least 3 months after a transfusion. Clinical data such as SCD-specific comorbidities and history of surgical splenectomy were also collected for all patients. A history of VTE was confirmed by radiography in the majority of cases. In cases where radiology was not available, only patients with a verified history of anticoagulation were included. Patients with a history of catheter-related VTE only were excluded (n=2). Results: Ninety-five patients with sickle variant genotypes had complete data and were included for analysis. The median age at follow-up was 42 years (range 21–72 years), and 55.8% of patients were female. Twenty-six (27.4%) patients had a history of VTE, 28.6% (8/28) with Sβ+thalassemia genotype and 26.9% (18/67) with SC genotype. Patients with a history of VTE had higher baseline hemoglobin levels compared to those without history of clot (11.6 g/dL vs. 10.8 g/dL, p<0.001). Additional laboratory parameters, including baseline WBC, platelet levels, and reticulocyte counts, did not significantly correlate to a history of VTE. A history of splenectomy was noted in 26.9% (7/26) of patients with VTE, 4 of whom developed a pulmonary embolism (PE) only, 2 of whom had a history of both deep venous thrombosis (DVT) and PE, and 1 of whom experienced an abdominal vein thrombosis. Splenectomy was significantly correlated to VTE on bivariate analysis (p=0.001), whereas other prevalent comorbidities such as avascular necrosis and retinopathy did not appear to be associated with VTE. On multivariate analysis controlling for demographics and genotype, older age (odds ratio (OR) 1.05, 95% confidence interval (CI) 1.01–1.10, p=0.015), hemoglobin level (OR 3.82, CI 1.83–7.98, p<0.001) and history of splenectomy (OR 4.93, CI 1.10–22.14, p=0.038) were found to be independent risk factors for VTE in our cohort. On subgroup analysis by VTE type, increased hemoglobin level persisted as a risk factor for both DVT (OR 5.69, CI 2.04–15.83, p=0.001) and PE (OR 3.55, CI 1.65–7.68, p=0.001), but splenectomy was statistically correlated to PE only (OR 4.79, CI 1.05–21.78, p=0.043). Conclusions: In patients with SC and Sβ+ thalassemia genotypes, VTE is common complication and is associated with higher baseline hemoglobin levels. In addition, splenectomy appears to be a risk factor for VTE, and specifically PE, in this population. These findings suggest that increased whole blood viscosity and surgical splenectomy may play a role in the development of venous thrombosis in SCD. Further studies will be needed to determine if functional asplenia is also associated with VTE in patients with sickle cell variant genotypes, and whether laboratory parameters can be used to predict VTE risk in SCD. Disclosures: Naik: NHLBI (K12): Research Funding. Streiff:sanofi-aventis: Consultancy, Honoraria; BristolMyersSquibb: Research Funding; Eisai: Consultancy; Janssen Healthcare: Consultancy; Daiichi-Sankyo: Consultancy. Lanzkron:Hemaquest: Membership on an entity's Board of Directors or advisory committees; NHLBI: Research Funding.

scholarly journals Alkaline Phosphatase Is Associated with Red Cell Alloimmunization in the Pulmonary Hypertension and Hypoxic Response (PUSH) Sickle Cell Disease Cohort

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 20-20
Author(s):  
Victoria Brooks ◽  
Oluwalonimi Adebowale ◽  
Victor R. Gordeuk ◽  
Sergei Nekhai ◽  
James G. Taylor
Keyword(s):  
Risk Factors ◽  
Alkaline Phosphatase ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Research Funding ◽  
Severe Disease ◽  
Case Control ◽  
Red Cell ◽  
Cell Disease ◽  
History Of

Background: Blood transfusion is a common therapy for sickle cell disease (SCD). Although, highly effective, a major limitation is development of alloantibodies to minor blood group antigens on donor red cells. Alloimmunization has a prevalence of 2-5% for transfusions in the general population, but it is significantly higher in SCD. Risk factors for alloimmunization have been poorly characterized, although number of lifetime transfusions is an important risk factor. Alloimmunization has been clinically observed in children with a prevalence of about 7%. With development of each antibody, blood donor matching becomes increasingly difficult and expensive with an increased risk for transfusion reactions and diminished availability of compatible red cell units for treatment of SCD. The ability to identify risk factors for developing alloantibodies would be beneficial for clinicians. To identify markers for alloimmunization in SCD, we have analyzed children and adults who developed this complication. Methods: We analyzed The Pulmonary Hypertension and Hypoxic Response in Sickle Cell Disease (PUSH) study, which enrolled n=468 pediatric and n=59 adult SCD subjects. In both children and adults, alloimmunization cases were defined as a history of at least 1 alloantibody. Controls in both cohorts were defined as subjects with no history of alloantibodies and receipt of more than 10 lifetime red cell transfusions. All others within the study who did not meet these criteria were assigned to a third comparison group. To identify differences between cases, controls and all others, we performed univariate analyses (using ANOVA or Kruskal Wallace where appropriate) for clinical parameters and laboratories. Case control comparisons were also performed for selected variables and plasma levels for 11 cytokines. Results were further analyzed using regression modeling. Results: The overall prevalence of alloimmunization was 7.3% among children (34/468 subjects; median age 12, range 3-20 years) compared to 28.8% in adults (17/59 subjects; median age 37, range 18-73 years). When only considering those with &gt;10 lifetime transfusions, the prevalence was considerably higher at 29.3% and 54.8% in children and adults, respectively. At the same time, 8 pediatric (23.5%) and 5 adult (29.4%) alloimmunization cases had received fewer than 10 transfusions. In a 3-way pediatric cohort comparison (cases, controls and all others), risk factors associated with alloimmunization included SS genotype, older age and markers of more severe disease (higher ferritin, WBCs, platelets and total bilirubin). Comparison of cases to controls showed alkaline phosphatase (P=0.05) was significantly lower in cases, whereas AST (P=0.02) was significantly higher even with adjustment for age. Levels of plasma cytokines MCP-1 (P=0.01) and IFNgamma (P=0.08) were lower in cases from a subset of the pediatric cohort. In adults, only 4/59 (6.8%) subjects had never received a lifetime transfusion (all non-SS). In the adult 3-way comparisons, only SS genotype and higher ferritin were associated with alloimmunization. The adult case control analysis showed higher absolute monocyte count (P=0.02), absolute eosinophil count (P=0.04) and absolute basophil count (P=0.008) in association with alloimmunization cases. In addition, alkaline phosphatase was again significantly lower among cases (P=0.02) as seen in the pediatric cohort. There were no significant differences in cytokine levels among adults. Conclusions: When considering only transfused SCD patients, the prevalence of alloimmunization is higher than 30%. As seen in prior studies, higher lifetime red cell transfusions are an important risk factor especially among adults where most patients have received transfusions. Children who develop alloantibodies appear to have laboratory markers of more severe disease, but this is not observed in adults. A novel association observed across both pediatric and adult subjects is a significantly lower serum alkaline phosphatase in those with alloantibodies. The results of this study suggest a need for improved tracking of red cell transfusion therapy in the US for SCD patients due to a high prevalence of alloimmunization. Further study is also needed to elucidate the significance of the alkaline phosphatase association. Disclosures Gordeuk: CSL Behring: Consultancy, Research Funding; Global Blood Therapeutics: Consultancy, Research Funding; Novartis: Consultancy; Ironwood: Research Funding; Imara: Research Funding.

scholarly journals Incidence, Management and Outcomes of Arterial and Venous Thromboembolism after Chimeric Antigen Receptor Modified T Cells for B-Cell Lymphoma and Multiple Myeloma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 7-7
Author(s):  
Anna L. Parks ◽  
Swetha Kambhampati ◽  
Bita Fakhri ◽  
Charalambos Andreadis ◽  
Lissa Gray ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Myeloma ◽  
T Cells ◽  
Venous Thromboembolism ◽  
B Cell ◽  
Research Funding ◽  
Vte Prophylaxis ◽  
Therapeutic Anticoagulation ◽  
Car T ◽  
History Of

Introduction: Chimeric antigen receptor modified T Cell (CAR-T) therapy is a rapidly developing treatment for patients with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (NHL) or multiple myeloma (MM). Although this population is at high risk for thrombosis, there are few data about rates of venous thromboembolism (VTE) and arterial thromboembolism (ATE) with CAR-T. Additionally, treatment with anticoagulation is complicated because of the prevalence of thrombocytopenia following CAR-T. Our goal was to determine the incidence, associated risk factors, management and outcomes of VTE and ATE in the 60 days following CAR-T therapy. Methods: We performed a single-center, retrospective cohort study of all patients who received inpatient CAR-T cells at UCSF Medical Center between January 2018 and May 2020 for R/R NHL or MM as standard-of-care or on a clinical trial. The outcomes of incident VTE and ATE were identified by ICD-10 codes and medical record review. Patient characteristics, pre-existing thrombosis risk factors, laboratory results, medications, and major or clinically relevant non-major bleeding or recurrent thrombotic complications were obtained through chart review. We used descriptive statistics to delineate risk factors, incidence, management and outcomes of thrombotic events. Results: Ninety-one patients who underwent CAR-T therapy were included in the analysis, 37 with NHL and 54 with MM. For NHL, mean age was 63 (range 38-82), and 41% were women. For MM, mean age was 62 (range 33-77), and 50% were women. Patients with NHL were treated with either investigational or Federal Drug Administration-approved CD19-directed therapies, and patients with MM were treated with a variety of investigational B-cell maturation antigen-directed (BCMA) therapies. For thrombotic risk factors, 13% of patients with NHL had a history of VTE, 3% had a history of ATE, 27% had a BMI ≥30, 59% had a recent procedure including central venous catheter (CVC) placement, 14% had an intensive care unit (ICU) stay, and 22% had an infectious complication in the 30 days pre- or post-CAR-T. Forty-one percent of patients with NHL had neurotoxicity of any grade, and 59% had CRS of any grade. At 30 days, 57% had a complete response, 41% had a partial response, 3% had stable disease. For MM, 6% of patients had a pre-existing history of VTE, 2% had a history of ATE, 19% had a BMI ≥30, 96% had a recent procedure, 11% had an ICU stay and 19% had an infection. Seventeen percent had neurotoxicity, and 85% had CRS. Thirty-two percent of patients with NHL and 48% with MM received pharmacologic VTE prophylaxis while undergoing CAR-T. For those who did not receive VTE prophylaxis, thrombocytopenia was the reason for holding prophylaxis, which occurred in 51% and 50% of NHL and MM patients, respectively. In the 60 days post-CAR-T, 4 (11%) patients with NHL were diagnosed with VTE-3 pulmonary embolism (PE) and 1 lower extremity deep vein thrombosis (DVT) associated with a previously placed inferior vena cava filter. Four (7%) patients with MM were diagnosed with VTE-1 PE and 3 upper extremity DVTs associated with CVCs. Five out of these 8 (63%) patients had symptomatic VTE, while the remainder were incidental on PETCT. Mean time from CAR-T infusion to VTE diagnosis was 20 days (range 6-39 days). There were no documented ATEs. Six out of 8 (75%) were treated with therapeutic anticoagulation. Of those who were anticoagulated, 4 patients received direct oral anticoagulants and 2 received low-molecular-weight-heparin. Duration was 3 months in 3 patients, 11 days in 1, 150 days in 1, and indefinitely in 1 with atrial fibrillation. Among all 8 patients with VTE, there were no bleeding events or recurrent thromboses regardless of whether or not they received anticoagulation. Discussion: In this cohort of patients with R/R NHL or MM who received either CD19- or BCMA-directed therapies, almost 1 in 10 developed VTE in the 60 days post-CAR-T. This occurred in the context of a high prevalence of risk factors for thrombosis and low rates of pharmacologic prophylaxis. Among those who developed VTE, the majority were treated with therapeutic anticoagulation for at least 3 months, without documented bleeding or recurrent VTE. Our findings provide crucial information on a common complication that can inform patients, clinicians and researchers and should be expanded upon in larger, prospective studies to identify optimal preventive and therapeutic strategies. Disclosures Fakhri: University of California San Francisco: Current Employment. Andreadis:Jazz Pharmaceuticals: Honoraria; Karyopharm: Honoraria; Incyte: Consultancy; Merck: Research Funding; Gilead/Kite: Consultancy; Novartis: Research Funding; BMS/Celgene/Juno: Honoraria, Research Funding; Genentech: Consultancy, Current equity holder in publicly-traded company. Wong:Janssen: Research Funding; Amgen: Consultancy; Roche: Research Funding; Fortis: Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Research Funding; GSK: Research Funding. Shah:BMS, Janssen, Bluebird Bio, Sutro Biopharma, Teneobio, Poseida, Nektar: Research Funding; GSK, Amgen, Indapta Therapeutics, Sanofi, BMS, CareDx, Kite, Karyopharm: Consultancy.

The risk of venous thrombosis in individuals with a history of superficial vein thrombosis and acquired venous thrombotic risk factors

Blood ◽  
2013 ◽  
Vol 122 (26) ◽  
pp. 4264-4269 ◽  
Author(s):  
Rachel E. J. Roach ◽  
Willem M. Lijfering ◽  
Astrid van Hylckama Vlieg ◽  
Frans M. Helmerhorst ◽  
Frits R. Rosendaal ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Venous Thrombosis ◽  
Superficial Vein ◽  
Thrombotic Risk ◽  
Vein Thrombosis ◽  
Thrombotic Risk Factor ◽  
Key Points ◽  
Superficial Vein Thrombosis ◽  
History Of

Key Points Superficial vein thrombosis combined with an acquired thrombotic risk factor increases the risk of venous thrombosis 10- to 100-fold. If confirmed, these findings have important implications for the future prevention of venous thrombosis.

scholarly journals The Interaction of Sickle Cell Trait and Anticardiolipin Antibodies in Venousthromboembolism

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4261-4261
Author(s):  
Chinedu A Ezekekwu ◽  
Taiwo R Kotila ◽  
Chinonso Chiemeka Anyanwu-Yeiya ◽  
Titilola S. Akingbola ◽  
Bamidele Tayo
Keyword(s):  
Risk Factors ◽  
Pulmonary Embolism ◽  
Venous Thromboembolism ◽  
Venous Thrombosis ◽  
Sickle Cell ◽  
Antiphospholipid Antibodies ◽  
Sedentary Lifestyle ◽  
Sickle Cell Trait ◽  
Anticardiolipin Antibodies ◽  
The Mean

Abstract Introduction Among the risk factors for venous thromboembolism (VTE) are inheritance of the sickle cell gene and antiphospholipid syndrome. Antiphospholipid antibodies are elevated in sickle cell disease but there is little information on its levels in sickle cell trait. The prevalence of anticardiolipin antibodies and association with VTE is equally not known in the Nigerian population. Methods A case control study involving 50 consecutive patients with Doppler confirmed venous thromboembolism at the University College Hospital Ibadan and 50 apparently healthy individuals. Haemoglobin electrophoresis was carried out using cellulose acetate membrane. IgG and IgM anticardiolipin antibodies were assayed by ELISA. Results The mean age of the patients was 58.7±18.5years, range of 21-89 years, there were 21 males (42%). Majority of the patients (42 (84%)) had deep venous thrombosis while five (10%) patients presented with pulmonary embolism, one had both deep venous thrombosis and pulmonary embolism. A patient had portal vein thrombosis and another, an intracardiac clot. Sedentary lifestyles, hypertension and concomitant malignancy were the most prevalent risk factors (34% each) (figure I). Both sedentary lifestyle and cancer were significantly associated with VTE (p&lt;0.001). Sickle cell trait (Hb AS) occurred in the same number of patients and controls (eleven each). Higher levels of both IgG and IgM anticardiolipin antibodies were found among the VTE patients with sickle cell trait than controls. (Table 1) The mean levels of IgG antibody in Hb AS patients was 31.7 ± 12.8 GPL compared to 25 ± 13.8 GPL in the controls (p= 0.254) and mean IgM anticardiolipin antibodies in Hb AS patients was 18.7 ± 6.2 GPL while that of the controls was 16.8 ± 11.6 GPL (p= 0.633). The global mean levels of IgG and IgM anticardiolipin antibodies in the patients with VTE were 29.7 ± 9.1 GPL and 24.8 ±16.7 GPL respectively versus 28.5 ±13.7 GPL and 25.2 ±16.2 GPL in the controls. A multivariable logistic regression showed age, sedentary lifestyle and anemia as independent risk factors while a positive IgM anticardiolipin antibody appeared protective for VTE. (Table 2) Conclusion The prevalence of sickle cell trait and anticardiolipin levels did not differ between VTE patients and healthy controls. Age, hypertension, sedentary lifestyle and malignancies were identified risk factors in our cohort of patients. Larger prospective studies may be helpful in determining the influence of sickle cell trait and antiphospholipid antibodies in venous thromboembolism. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Risk Factors for Adverse Maternal and Fetal Outcomes in Pregnant Patients with Sickle Cell Disease

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3117-3117
Author(s):  
Sherraine Della-Moretta ◽  
William Marshall ◽  
Rui Li ◽  
Erin Cleary ◽  
Philip Samuels ◽  
...  
Keyword(s):  
Risk Factors ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Research Funding ◽  
Maternal Age ◽  
Acute Chest Syndrome ◽  
Hypertensive Disorders Of Pregnancy ◽  
Cell Disease ◽  
History Of ◽  
Maternal Bmi

Abstract Background Approximately 100,000 Americans are affected by sickle cell disease (SCD), an inherited hematologic disorder. In women with sickle cell disease, pregnancy is associated with increased maternal and fetal adverse outcomes (Elenga et al). However, there is a paucity of data on risk factors for adverse events in this population. This retrospective study seeks to add to the deficient repertoire of information regarding maternal and fetal outcomes in patients with sickle cell disease and their children. Methods We retrospectively evaluated pregnancy outcomes of women with SCD who had previously undergone echocardiography from the year 2000-2021. The associations between clinical variables and adverse hematologic (AHE), cardiac (ACE), obstetric (AOE) and fetal/neonatal (ANE) events were evaluated by the Generalized Linear Model (GLM). The adverse hematologic events were vaso-occlusive crisis (VOC) antepartum and postpartum, acute chest syndrome, venous thromboembolism antepartum and postpartum, and transfusion antepartum. Results We identified 43 women/59 pregnancies with a median maternal age 27 years old (interquartile range [IQR] 20), pre-pregnancy BMI 25 kg/m2 (IQR 16). Maternal sickle cell genotype was SS in 31 (72%) women/37 (63%) pregnancies, SC in 8 (18%) women/18 (31%) pregnancies, and other genotype in 4 (9%) women/4 (7%) pregnancies. Prior venous thromboembolism was present in 12 (27%) women/15 (25%) pregnancies and prior acute chest syndrome (ACS) in 33 (80%) women/41 (75%) pregnancies. In the year before pregnancy, 24 (56%) women were admitted at least once for VOC. There were no maternal deaths during pregnancy or up to 1 year postpartum. AHE (n = 171) occurred in 43 (73%) pregnancies (Figure A), with a median of 2 (range 0-13) AHE per pregnancy. AHE were more common with genotype SS, history of ACS, history of ³ 10 lifetime transfusions, admission for VOC in the year before pregnancy, tricuspid regurgitation velocity (TRV) &gt;2.5 m/s on echocardiogram, and increased maternal age, and less common with increased hemoglobin (Figure B). ACE were rare (n = 3) (Figure A) and weakly associated with increased maternal age (Figure C). AOE (n = 37) occurred in 27 (45%) pregnancies (Figure A) and were associated with lower pre-pregnancy maternal BMI (Figure D). ANE (n = 54) occurred in 27 (46%) of pregnancies, and were associated with maternal hypertensive disorders of pregnancy (Figure E). Conclusions We found that AHE during pregnancy in women with SCD were associated with genotype SS, history of ACS, ³ 10 lifetime transfusions, admission for VOC in the year before pregnancy, higher maternal age, and inversely related to hemoglobin. In addition, AHE during pregnancy were associated with TRV &gt;2.5 m/s on echocardiogram, which has not been previously shown in women with SCD. These data may be useful to identify women at increased risk during pregnancy. Data show that patients with sickle cell disease who have more disease-related complications including history of acute chest syndrome, frequent pain crisis, elevated TRV on echocardiogram, and lower hemoglobin are at greater risk for AHE. This suggests that disease severity is directly related to outcomes. The association between increased maternal age and ACE has been demonstrated in the past in women without SCD (DeViti et al). The same can be noted for the association of AOE with lower maternal BMI (Verma et al), and ANE being associated with maternal hypertensive disorders of pregnancy (Lugobe et al). In the future, prevention of these complications will be key. Future directions include determining the effect of disease-modifying therapy on these outcomes, though safety during pregnancy has not yet been demonstrated for more novel agents such as voxelotor and crizanlizumab. With more information on these risk factors, we hope that modification and treatment can result in better outcomes. Figure 1 Figure 1. Disclosures Desai: Pfizer: Other: Publication Fee, Research Funding; Foundation for Sickle Cell Research: Honoraria; Forma: Consultancy; Novartis: Research Funding, Speakers Bureau; Global Blood Therapeutics: Honoraria, Research Funding.

scholarly journals Cerebral Venous Sinus Thrombosis (CVST) in a Middle-Aged Female with Clustering of Risk Factors

2021 ◽  
Vol 10 (34) ◽  
pp. 2960-2963
Author(s):  
Maria Prothasis ◽  
Yash Gupte ◽  
Sourya Acharya ◽  
Samarth Shukla ◽  
Neema Acharya
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Venous Thromboembolism ◽  
Venous Thrombosis ◽  
Cerebral Venous Thrombosis ◽  
Sinus Thrombosis ◽  
Cerebral Venous Sinus Thrombosis ◽  
Venous Sinus ◽  
Factor V ◽  
Venous Sinus Thrombosis

Thrombosis of cerebral venous channel is a known complication of hypercoagulable states. Hyperhomocysteinaemia is a known hypercoagulable state. Obesity is a modern-day global epidemic. Disorders such as myocardial infarction (MI), stroke, and venous thromboembolism are on the rising trend and its increased morbidity and mortality is being associated with obesity. To date, however, the knowledge about the association between obesity and adult cerebral venous thrombosis (CVT) is sparse. We report a 44-year-old young morbidly obese metabolically unhealthy female who presented with headache, nausea, vomiting and giddiness. On evaluation, magnetic resonance venogram showed cerebral venous sinus thrombosis. On investigations, she had concomitant hyperhomocysteinaemia and metabolic syndrome. Cerebral venous sinus thrombosis causing stroke in young adults is uncommon with various conditions precipitating it.1,2,3 Severe headache (70 - 90 %), focal lateralized signs (25 % - 75 %), seizures (30 – 40 %) as well as behavioural symptoms such as delirium, amnesia, and disturbances in consciousness are the various associated clinical symptoms. The known inherited hypercoagulable risk factors that cause CVST are gain of function mutations in the genes encoding factor V (factor V Leiden) and prothrombin, Protein C, S and antithrombin III deficiency. Hyperhomocysteinaemia, is a known risk factor for causing venous thrombosis of the lower limbs. However, till date there is no data available showing its role in causing cerebral venous thrombosis. The interaction between genetic and acquired determinants result in high plasma levels of total homocysteine (tHcy).4,5,6 Vitamins such as folic acid, pyridoxine, and cobalamin are involved in the metabolic pathways of homocysteine and its deficiencies represent the acquired determinants. Venous thromboembolism (VTE) comprises of deep vein thrombosis of the leg and pulmonary embolism and obesity is now being recognised as one of the risk factors causing it. The risk of VTE is approximately increased to 2-fold in an individual with a body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) of 30 or more compared with a normal BMI (< 25), and higher BMIs increase more risk with approximately 3 times higher risk in individuals with a BMI greater than 40.7, 8,9 Again obesity as a risk factor for CVST is less known.

Assessment of Clinical Risk Factors for Symptomatic Venous Thromboembolism in Common Cancers: A VERITY Registry Study

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3826-3826
Author(s):  
Shankaranarayana Paneesha ◽  
Aidan McManus ◽  
Roopen Arya ◽  
Nicholas Scriven ◽  
Tim Nokes ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Risk Factors ◽  
Risk Factor ◽  
Venous Thromboembolism ◽  
Family History ◽  
Cancer History ◽  
Patients With Cancer ◽  
Thrombosis Risk ◽  
History Of ◽  
Age And Sex

Abstract The association between venous thromboembolism (VTE) and cancer is well-recognised, but the thrombosis risk factor profile of patients with cancer-associated VTE is poorly characterised; it is unclear if additional risk factors contribute to the risk of thrombosis beyond the cancer itself, or if the risk factor profile is tumour-specific. Our aim was to compare the thrombosis risk factor profiles of cancer patients with or without symptomatic VTE enrolled in VERITY, an ongoing UK prospective VTE registry. The VERITY registry records data on patients with VTE and those in whom the diagnosis of VTE is excluded. Between Jun 05 and Mar 08, 49044 patient entries were made. Individual case data for patients with cancer were extracted. Using available risk factor data, univariate analysis of 9 established risk factors for VTE (medical in-patient history/immobilisation >3 days within last 4 weeks; major surgery in the last 4 weeks; hormonal risk factor; previous history of VTE; family history of VTE; known thrombophilia; intravenous drug abuse; current smoking; and leg paralysis), comparing VTE and non-VTE cancer cases, was performed for the 4 most common cancers using SPSS. To account for the potential impact of age and sex on VTE risk, age-adjusted values were calculated for breast and prostate cancer, and age- and sex-adjusted values for colorectal and lung. A nominal level of 5% statistical significance was assumed. Of 2825 cancer cases, 1382 had an objectively confirmed diagnosis of VTE and in 1443 the diagnosis of VTE was excluded. Breast (n=498), prostate (n=374), colorectal (n=343) and lung cancer (n=275) accounted for 53% of cancer cases. Univariate associations between risk factors and symptomatic VTE were found only for prostate cancer: history of VTE (odds ratio [OR] = 3.48; 95% CI, 2.01, 6.02; p < 0.00001), family history of VTE (OR = 2.56; 95% CI, 1.02, 6.44; p = 0.046), hormonal risk factor (OR = 2.22; 95% CI, 1.00, 4.92; p = 0.049). In colorectal cancer, smoking was less likely in VTE cases (OR = 0.54; 95% CI, 0.34, 0.87; p = 0.012). Adjusting for age (and sex), univariate associations between risk factors and symptomatic VTE were again found only for prostate cancer: history of VTE (OR = 3.23; 95% CI, 1.56, 6.68; p = 0.002), with smoking less likely in age-adjusted VTE cases (OR = 0.50; 95% CI, 0.28, 0.91; p = 0.022). Our analysis of a registry population found few associations between known thrombosis risk factors and symptomatic VTE in patients with common cancers, suggesting these factors impact little on thromboembolic risk in these cancers.

Should Sickle Cell Disease be Among the Risk Factors for Use of Thromboprophylaxis in Adolescents and Young Adults ?

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4855-4855 ◽  
Author(s):  
Erin Morales ◽  
Gabriela Ines Villanueva ◽  
Lewis L. Hsu ◽  
Nili Seleski
Keyword(s):  
Risk Factors ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Research Funding ◽  
Pediatric Population ◽  
Multivariate Regression Analysis ◽  
Central Line ◽  
Cell Disease ◽  
Vte Prophylaxis ◽  
History Of

Abstract Introduction: As published by Naik both in single-institution and multi-institution data, adults with sickle cell disease have a baseline hypercoagulable state in addition to traditional risk factors. In pediatrics, venous thromboembolism (VTE) is often overlooked because of the low incidence in children. In addition, there is no unified consensus that supports the use of prophylaxis or screening of the pediatric population at risk. Although the incidence of VTE in the general pediatric population is low, there may be those children, including those with sickle cell disease (SCD), who would benefit from VTE prophylaxis. Objectives: Estimate the contribution of sickle cell disease to rates of VTE in adolescents and young adults, compare rates of prophylaxis in the pediatric units versus the adult units, and determine risk factors associated with VTE occurrence in a hospital serving a large population with sickle cell disease. Methods: This study was a retrospective chart review of patients aged 14-25 admitted to the Pediatric Intensive Care Unit (PICU), to the Pediatric Sickle Cell Service, and to the Medical Intensive Care Unit (MICU) between the dates of April 1, 2014 and April 30, 2015. Anyone older than age 18 admitted to the PICU or Pediatric Sickle Cell Service was considered part of pediatrics. Charts were searched manually for incidence of VTE during hospitalization, risk factors for developing VTE, history of prior VTE, use of therapeutic anticoagulation, and prophylaxis use and type. Data was analyzed using a multivariate regression analysis. Results: In the 13-month period, 251 AYA admissions (108 to the PICU and 143 to the Sickle cell Unit) and 67 MICU admissions were reviewed. 66/67 (99%) MICU patients received either chemical or mechanical prophylaxis against VTE compared to 9/251 (3.5%) children. Event rates of VTE were 3/67 (4.5%) in MICU and 2/251 (0.8%) in the Pediatric units - 1 in the Sickle Cell unit and 1 in the PICU. In the pediatric units, none of the patients receiving prophylaxis had an acute VTE and both patients with VTE were not on prophylaxis. Both adolescents had central lines in place at the time of VTE occurrence. Of the MICU events, one patient had SCD and was taking systemic anticoagulation for previous VTE but had a central line in place. The other MICU patients both had infections, one with Crohns Disease and the other with a central line placed (table 2). The multivariate regression analysis demonstrated that prior history of a VTE and prolonged LOS were positively correlated with increased risk for VTE, both with a confidence interval of 95% and a corrected critical value of 0.003 using the Bonferroni correction (table 1). Conclusion: Of the 5 VTE events in the 318 AYA hospitalizations reviewed, two (40%) were in patients with SCD (ages 17 and 24). As expected, overall VTE incidence in AYA is low in our institution, and appear to be associated with heightened inflammation and central line placement. VTE events in the pediatric unit were in patients not receiving any prophylaxis, which is not surprising when VTE prophylaxis orders were rare on the pediatric units (3.5%). In both our pediatric unit cases, prophylaxis may have prevented the VTE. A consensus protocol to identify high risk children is being implemented and refined with ongoing data collection. The data from our hospital AYA population enriched in SCD reinforces previous data from adult sickle cell populations that the magnitude of VTE risk attributable to SCD can be high. SCD probably should be among the screening criteria when deciding VTE prophylaxis in hospitalized adolescents. Disclosures Hsu: Purdue Pharma: Research Funding; Gerson Lehman Group: Consultancy; Hilton Publishing: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Astra Zeneca: Consultancy, Research Funding; Eli Lilly: Research Funding; Sancilio: Research Funding; Centers for Medicare and Medicaid Innovation: Research Funding; EMMI Solutions: Consultancy; Mast Therapeutics: Research Funding.

Family history of venous thrombosis or sudden death as a risk factor for venous thromboembolism

2012 ◽  
Vol 107 (06) ◽  
pp. 1191-1192 ◽  
Author(s):  
Paolo Prandoni ◽  
Martin Prins ◽  
Angelo Ghirarduzzi ◽  
Vittorio Pengo ◽  
Maria Sartori ◽  
...  
Keyword(s):  
Risk Factor ◽  
Venous Thromboembolism ◽  
Family History ◽  
Sudden Death ◽  
Venous Thrombosis ◽  
History Of

scholarly journals Risk of future arterial cardiovascular events in patients with idiopathic venous thromboembolism

Hematology ◽  
2009 ◽  
Vol 2009 (1) ◽  
pp. 259-266 ◽  
Author(s):  
David Green
Keyword(s):  
Myocardial Infarction ◽  
Risk Factor ◽  
Venous Thromboembolism ◽  
Venous Thrombosis ◽  
Arterial Thrombosis ◽  
Coronary Calcification ◽  
Arterial Disease ◽  
Venous Disease ◽  
Clotting Factors ◽  
History Of

Abstract Venous and arterial thromboses have traditionally been considered distinct pathophysiologic entities. However, the two disorders have many features in common, and there is evidence that persons with venous thrombosis may be at greater risk for arterial events. The pathogenesis of both disorders includes endothelial injury, platelet activation, elevated levels of intrinsic clotting factors and inflammatory markers, increased fibrinogen, and impaired fibrinolysis. In addition, older age, obesity, dyslipidemia, and smoking predispose to both venous and arterial thrombosis. While the evidence that arterial disease is a risk factor for venous thrombosis is inconclusive, arterial disease does appear to occur with a modestly increased frequency in patients with a history of venous thromboembolism. Reported odds ratios in such patients were 1.2 for myocardial infarction, 1.3 for stroke, 2.3 for carotid plaque, and 4.3 for coronary calcification. Of note, in persons under age 40 with unprovoked venous thrombosis, the odds ratio for acute myocardial infarction was as high as 3.9. In general, however, venous disease is considered to be a weak risk factor for arterial thrombosis, and the use of agents specifically targeted to the prevention of heart attack or stroke in the majority of persons with VTE cannot be recommended at present.

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