Usefulness of antithrombin deficiency phenotypes for risk assessment of venous thromboembolism: type I deficiency as a strong risk factor for venous thromboembolism

2010 ◽  
Vol 92 (3) ◽  
pp. 468-473 ◽  
Author(s):  
Mana Mitsuguro ◽  
Toshiyuki Sakata ◽  
Akira Okamoto ◽  
Sachika Kameda ◽  
Yoshihiro Kokubo ◽  
...  
2020 ◽  
Vol 7 (4) ◽  
pp. e320-e328 ◽  
Author(s):  
Maria Abbattista ◽  
Francesca Gianniello ◽  
Cristina Novembrino ◽  
Marigrazia Clerici ◽  
Andrea Artoni ◽  
...  

Blood ◽  
1999 ◽  
Vol 94 (8) ◽  
pp. 2590-2594 ◽  
Author(s):  
H.H. van Boven ◽  
J.P. Vandenbroucke ◽  
E. Briët ◽  
F.R. Rosendaal

To analyze inherited antithrombin deficiency as a risk factor for venous thromboembolism in various conditions with regard to the presence or absence of additional genetic or acquired risk factors, we compared 48 antithrombin-deficient individuals with 44 nondeficient individuals of 14 selected families with inherited antithrombin deficiency. The incidence of venous thromboembolism for antithrombin deficient individuals was 20 times higher than among nondeficient individuals (1.1% v 0.05% per year). At the age of 50 years, greater than 50% of antithrombin-deficient individuals had experienced thrombosis compared with 5% of nondeficient individuals. Additional genetic risk factors, Factor V Leiden and PT20210A, were found in more than half of these selected families. The effect of exposure to 2 genetic defects was a 5-fold increased incidence (4.6% per year; 95% confidence interval [CI], 1.9% to 11.1%). Acquired risk factors were often present, determining the onset of thrombosis. The incidence among those with exposure to antithrombin deficiency and an acquired risk factor was increased 20-fold (20.3% per year; 95% CI, 12.0% to 34.3%). In conclusion, in these thrombophilia families, the genetic and environmental factors interact to bring about venous thrombosis. Inherited antithrombin deficiency proves to be a prominent risk factor for venous thromboembolism. The increased risks among those with exposure to acquired risk factors should be considered and adequate prophylactic anticoagulant therapy in high-risk situations seems indicated in selected families with inherited antithrombin deficiency.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4215-4215
Author(s):  
Edward M. Peres ◽  
Alex Orman ◽  
Shin Mineishi ◽  
Denise Markstrom ◽  
Paula Bockenstedt ◽  
...  

Abstract Abstract 4215 Background: Individuals with hematologic malignancies, are at high risk for Venous thromboembolism (VTE). In patients undergoing hematopoietic stem cell transplantation (HSCT) the incidence and risk of VTE is unclear. Based on this it is difficult to consider prophylaxis in patients who are at potentially high risk for bleeding complications (Gerber, Blood 2008). It is increasingly becoming important to measure the risks of VTE, as the incidence has continued to rise. Different scoring systems have been proposed to assess the risks of VTE in hospitalized patients. In patients who develop VTE during hospitalization their risk of morbidity and mortality is increased. We examined 286 patients who received autologous HSCT transplantation, and 343 patients who underwent allogenic HSCT transplantation at the University of Michigan. We then compared their scores based on the risk assessment score developed by Caprini et al (Ann. Of Surg. 2010). The scoring system was initially validated for patients undergoing surgical procedures, and is currently in use at the University of Michigan to asses risk in bone marrow transplant patients. Risks for the development of VTE range from 10–20% (for moderate risk), 20–40% (higher risk), and 40–80% (highest risk). Objectives: To evaluate the efficacy of Caprinis' risk factor assessment scoring system in patients undergoing autologous and allogenic HSCT and determining the incidence of VTE in the patient cohort. Methods: The medical records of 629 patients between 2005–2008 who received high dose chemotherapy followed by autologous (287) and allogenic (343) stem cell transplants were reviewed. The autologous patient cohort had a mean age of 48.9, and an average BMI of 29.01. The allogenic patient cohort had a mean age of 42.5, with an average BMI of 27.53. HSCT was performed for all of the following conditions: Non-Hodgkin's lymphoma, Neuroblastoma, Multiple myeloma, Leukemia, Myelodysplastic Syndrome, and Hodgkin's lymphoma. The scores were compiled on the day of admission or at the closest date to the actual stem-cell transplant. Based on scoring, the actual incidence of non catheter related VTE in the HSCT patient population was observed. Allogenic patients were observed for VTE incidence from admission to day 30, day 30–100, and 100 days and on. Autologous patients were observed from admission to day 30. Results: 1) Of the 286 patients receiving autologous transplantation the average Caprini risk assessment score was 6.4. The 343 patients receiving allogenic transplantation had an average score of 5.95. Twenty-seven autologous, and fifty-three allogenic patients were at higher risk (3-4 point range) with a 20–40% chance of developing a VTE. 259 autologous patients, and 287 allogenic patients were at the highest risk (5+ point range) with a 40–80% chance of developing a VTE. 2) In both patient cohorts, based on the Caprini risk assessment score HSCT patients were placed in the highest risk category with a 40–80% chance of developing a VTE. 3) Only two patients (0.69%) developed an actual VTE during hospitalization for autologous HSCT. These patients both had a score of 10. Two patients (0.58%) receiving allogenic HSCT developed a VTE from the time of admission to 30 days. These patients had an average score of 7.5. From 30–100 days 5 patients deve loped a VTE, of these patients 1 developed CGVHD, The patients had an average score of 7.6. Twenty patients developed a VTE greater then 100 days, of these patients, 4 of which developed CGVHD. The patients had an average score of 6.55. Conclusion: The Caprini Venous Thromboembolism risk factor a ssessment score is not valid in patients undergoing high dose chemotherapy followed by an autologous or allogenic transplant. HSCT patients are at high risk for bleeding complications and the risk of VTE is relatively low (<1%). Only 2/286 (autologous transplant 0.69%) patients developed a VTE, and 2/343 (allogenic transplant) patients (0.58%) went on to develop a VTE. While VTE prophylaxis may be warranted in surgical and hospitalized patients, this study suggests it may not be necessary in patients undergoing HSCT who are at high risk of bleeding complication. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1056-1056
Author(s):  
Jan-Leendert P. Brouwer ◽  
Nic J.G.M. Veeger ◽  
Wim van der Schaaf ◽  
Hanneke C. Kluin-Nelemans ◽  
Jan van der Meer

Abstract A family cohort study was performed to assess the absolute risk of thromboembolism associated with inherited protein S (PS) deficiency type I and type III. Probands were consecutive patients with thromboembolism and either type I or type III deficiency. Of living first degree relatives (age&gt;15 years), 156 (90%) from type I deficient probands (cohort 1) and 268 (88%) from type III deficient probands (cohort 2) were analyzed. Annual incidences of venous thromboembolism were 1.47 and 0.17 in deficient and non-deficient relatives in cohort 1 (RR 8.9; 95% CI 2.6–30.0), and 0.27 versus 0.24 in cohort 2 (RR 0.9; 95% CI 0.4–2.2). The cut off level of free PS to identify subjects at risk was 30%. Lower levels were found in 40% and 1% of relatives in cohort 1 and 2, respectively. We demonstrated that the cut-off level of free PS is considerably lower than the lower limit of its normal range in healthy volunteers, that is commonly used (in our study 30% in stead of 65%). If we had used only a total PS assay, 8 (2%) relatives at risk would have been missed, but 67% (346/517) of relatives would not be tested. Only testing for free PS deficiency (free PS levels &lt;65%) would have increased the number of tested relatives, but 179 (35%) relatives would be wrongly classified as at risk. Neither type I nor type III deficiency were associated with arterial thromboembolism. In conclusion, inherited PS deficiency type I, but not type III showed to be a strong risk factor for venous thromboembolism. This difference was due to lower free PS levels in type I deficient subjects and a free PS cut-off level that was half of the lower limit of its normal range.


2000 ◽  
Vol 30 (2) ◽  
pp. 72-76 ◽  
Author(s):  
Hans-Martin M.B. Otten ◽  
Martin H. Prins ◽  
Susanne M. Smorenburg ◽  
Barbara A. Hutten

2014 ◽  
Vol 112 (09) ◽  
pp. 478-485 ◽  
Author(s):  
Verena Limperger ◽  
Andre Franke ◽  
Gili Kenet ◽  
Susanne Holzhauer ◽  
Ralf Junker ◽  
...  

SummaryVenous thromboembolism [TE] is a multifactorial disease and antithrombin deficiency [ATD] constitutes a major risk factor. In the present study the prevalence of ATD and the clinical presentation at TE onset in a cohort of paediatric index cases are reported. In 319 un - selected paediatric patients (0.1–18 years) from 313 families, recruited between July 1996 and December 2013, a comprehensive thrombophilia screening was performed along with recording of anamnestic data. 21 of 319 paediatric patients (6.6%), corresponding to 16 of 313 families (5.1%), were AT-deficient with confirmed underlying AT gene mutations. Mean age at first TE onset was 14 years (range 0.1 to 17). Thrombotic locations were renal veins (n=2), cerebral veins (n=5), deep veins (DVT) of the leg (n=9), DVT & pulmonary embolism (n=4) and pelvic veins (n=1). ATD co-occurred with the factor- V-Leiden mutation in one and the prothrombin G20210A mutation in two children. In 57.2% of patients a concomitant risk factor for TE was identified, whereas 42.8% of patients developed TE spontaneously. A second TE event within primarily healthy siblings occurred in three of 313 families and a third event among siblings was observed in one family. In an unselected cohort of paediatric patients with symptomatic TE, the prevalence of ATD adjusted for family status was 5.1%. Given its clinical implication for patients and family members, thrombophilia testing should be performed and the benefit of medical or educational interventions should be evaluated in this high risk population.


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