Thrombophilia Testing in Hospitalized Patients with Acute Ischemic Stroke: An Opportunity for Hematology Input

INTRODUCTION: Thrombophilia testing (TT) is ordered in acute ischemic stroke (AIS) in an attempt to diagnose rare hypercoagulable disorders, most notably antiphospholipid antibody syndrome (APS), as secondary stroke prevention may require anticoagulation in addition to antiplatelet therapy. Given the paucity of clinical evidence and the absence of formal guidelines, TT is frequently overused, resulting in excess health care costs and potential misinterpretation of results which may result in patient harm. Herein, we report the ordering practices and the effects of TT on outcomes in patients hospitalized for AIS at a large academic center, with the intent of identifying areas for intervention to improve TT stewardship. METHODS: Patients hospitalized for AIS between January, 2015, and January, 2017, were identified using ICD-10 codes, and those that received TT were identified using laboratory records. Demographic, medical history, stroke diagnostic workup, and TT characteristics were collected from medical records. Distribution of variables were reported using mean (SD) or median (IQR) for continuous variables and percentages for categorical variables. RESULTS: Of the 1900 patients admitted with AIS during this 2-year period, 190 (10%) underwent TT which included: lupus anticoagulant (100%), anticardiolipin IgG and IgM (97.9%), anti-beta-2-glycoprotein-1 IgG (81.6%) and IgM (78.9%), protein C (85.8%), protein S (86.3%), antithrombin (86.3%), factor VIII (84.2%), homocysteine (87.4%), prothrombin gene mutation (82.6%), and activated protein C resistance (83.2%). Of these, 137 (72.1%) had at least 1 abnormal result. However, when abnormal factor VIII (71.3% abnormal) was excluded, the percent with an abnormal result was 37%. Patients who underwent TT were younger compared to those who did not (mean age 47.3y, SD 13.8 vs. 64y, SD 15; p<.0001). Females were more frequently tested than males (60% vs. 40%). Testing of White and African American patients reflected the demographics of the stroke population (55.7% and 42.8%, respectively). Most tested patients (82%) had at least 1 cardiovascular disease risk factor based on the Framingham Heart Study risk algorithms. Elevated factor VIII constituted the most common abnormal test, followed by elevated homocysteine (19.9%) and low protein S (18.3%) (Fig 1), though this testing is not recommended during acute thrombosis. At least one assay for APS was positive in 3 patients (1.6%), which was repeated in only 1 patient after 12 weeks. Testing for APS was incomplete in 23% of patients, most frequently due to the omission of anti-beta-2-glycoprotein-1 antibodies. Only 16% of patients received inpatient or outpatient hematology input, all after the TT had been ordered. The average time between admission and TT was 1.79 days, with 68.4% of patients tested within 24 hours of admission, indicating that TT was reflexive and occurred prior to evaluation for cardiovascular risk factors. The indication that prompted TT was not documented in 75.3%; most commonly documented indications were younger age (8%), personal (5%) or family history of thrombosis (7.7%), and a history of a rheumatologic disorder (4%). Documentation of family history was incomplete or absent in 31% of tested patients. At discharge, the etiology of stroke was determined in 53.2% of the patients who underwent TT testing, while 46.8% remained undetermined. TT changed management in 4 patients (2%); 3 with APS and 1 with heterozygous factor V Leiden were started on anticoagulation. One patient subsequently developed a clinically relevant non-major bleeding and anticoagulation was discontinued. CONCLUSION: We found that TT is frequently obtained in hospitalized patients with AIS, often before evaluation for other traditional stroke risk factors has been performed. TT changed management in only 2% of tested patients and contributed to harm in 1 patient. Collaboration between hematologists and neurologists to improve TT stewardship is needed to curtail patient risk and unnecessary cost. In an effort to limit TT, we are increasing awareness through provider education, and have created an order set in the electronic medical record to encourage appropriate ordering practices and consultation with hematology in patients with AIS where TT is felt to be indicated. Disclosures No relevant conflicts of interest to declare.

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Modifiable and Non-Modifiable Risk Factors for Atherothrombotic Ischemic Stroke among Subjects in the Malmö Diet and Cancer Study

Nutrients ◽

10.3390/nu13061952 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1952

Author(s):

Anna Johansson ◽

Isabel Drake ◽

Gunnar Engström ◽

Stefan Acosta

Keyword(s):

Physical Activity ◽

Risk Factors ◽

Body Mass Index ◽

Ischemic Stroke ◽

Family History ◽

Diet Quality ◽

Alcohol Intake ◽

Modifiable Risk Factors ◽

History Of ◽

Diet And Cancer

Risk factors for ischemic stroke is suggested to differ by etiologic subtypes. The purpose of this study was to examine the associations between modifiable and non-modifiable risk factors and atherothrombotic stroke (i.e., excluding cardioembolic stroke), and to examine if the potential benefit of modifiable lifestyle factors differs among subjects with and without predisposing comorbidities. After a median follow-up of 21.2 years, 2339 individuals were diagnosed with atherothrombotic stroke out of 26,547 study participants from the Malmö Diet and Cancer study. Using multivariable Cox regression, we examined non-modifiable (demographics and family history of stroke), semi-modifiable comorbidities (hypertension, dyslipidemia, diabetes mellitus and atherosclerotic disease), and modifiable (smoking, body mass index, diet quality, physical activity, and alcohol intake) risk factors in relation to atherothrombotic stroke. Higher age, male gender, family history of stroke, and low educational level increased the risk of atherothrombotic stroke as did predisposing comorbidities. Non-smoking (hazard ratio (HR) = 0.62, 95% confidence interval (CI) 0.56–0.68), high diet quality (HR = 0.83, 95% CI 0.72–0.97) and high leisure-time physical activity (HR = 0.89, 95% CI 0.80–0.98) decreased the risk of atherothrombotic ischemic stroke independent of established risk factors, with non-significant associations with body mass index and alcohol intake. The effect of the lifestyle factors was independent of predisposing comorbidities at baseline. The adverse effects of several cardiovascular risk factors were confirmed in this study of atherothrombotic stroke. Smoking cessation, improving diet quality and increasing physical activity level is likely to lower risk of atherothrombotic stroke in the general population as well as in patient groups at high risk.

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Abstract P686: Ischemic Stroke in Reversible Cerebral Vasoconstriction Syndrome

Stroke ◽

10.1161/str.52.suppl_1.p686 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Aayushi Garg ◽

Amjad Elmashala ◽

Santiago Ortega

Keyword(s):

Risk Factors ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Survey Design ◽

Inpatient Rehabilitation ◽

Reversible Cerebral Vasoconstriction Syndrome ◽

Hospital Charges ◽

Multivariable Logistic Regression Analysis ◽

Cerebral Vasoconstriction ◽

History Of

Introduction: Ischemic stroke is the cause for major morbidity and mortality in reversible cerebral vasoconstriction syndrome (RCVS). While there is evidence to suggest that ischemic stroke in RCVS is associated with proximal vasoconstriction, it is still unclear why some patients develop ischemic lesions. The aim of this study was to evaluate the risk factors and outcomes of ischemic stroke in RCVS. Methods: We utilized the Nationwide Readmissions Database 2016-2017 to identify all hospitalizations with the discharge diagnosis of RCVS. Occurrence of acute ischemic stroke was identified. Hospitalizations with the diagnosis of hemorrhagic stroke were excluded. Survey design methods were used to generate national estimates. Independent predictors of ischemic stroke were analyzed using multivariable logistic regression analysis with results expressed as odds ratio (OR) and 95% confidence intervals (CI). Results: Among the total 1,065 hospitalizations for RCVS during the study period (mean±SD age: 49.0±16.7 years, female 69.7%), 267 (25.1%) had occurrence of acute ischemic stroke. Patients with ischemic stroke were more likely to have history of hypertension (OR 2.33, 95% CI 1.51-3.60), diabetes (OR 1.81, 95% CI 1.11-2.98), and tobacco use (OR 1.64, 95% CI 1.16-2.33) and less likely to have a history of migraine (OR 0.56, 95% CI 0.35-0.90). Patients with stroke were more likely to develop cerebral edema. They also had longer hospital stay, higher hospital charges, and lower likelihood of being discharged to home or inpatient rehabilitation facility. They had higher in-hospital mortality rate, the difference was however not statistically significant. Conclusion: In conclusion, ischemic stroke affects nearly 25% of patients with RCVS and is associated with an increased rate of other neurologic complications and worse functional outcomes. Patients with traditional cerebrovascular risk factors might have a higher predisposition for developing the ischemic lesions.

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Appropriateness of Thrombophilia Testing in Tertiary Care Centers in Edmonton

Blood ◽

10.1182/blood.v126.23.4470.4470 ◽

2015 ◽

Vol 126 (23) ◽

pp. 4470-4470

Author(s):

Alabdurubalnabi Zainab ◽

Salma Shivji ◽

Cynthia Wu

Keyword(s):

Family History ◽

Board Of Directors ◽

Protein C ◽

Protein S ◽

Test Results ◽

Advisory Committees ◽

Increased Risk ◽

History Of ◽

Thrombophilia Testing

Abstract INTRODUCTION Thrombophilia is associated with an increased risk of venous thromboembolism (VTE). Despite this link, determining the presence or absence of such conditions has no role in VTE management including determining the choice or duration of anticoagulant therapy. Testing can be potentially harmful when results are misinterpreted or impact patient anxiety and insurance eligibility. METHODS We performed a retrospective chart review of adult patients presenting to the emergency department (ED) or were admitted to the University of Alberta Hospital (UAH), Royal Alexandra Hospital (RAH) and Grey Nuns Hospital (GNH) and underwent any number of thrombophilia tests (including factor V Leiden [FVL], prothrombin gene mutation [PT20210], protein C [PC], protein S [PS], antithrombin [AT] and antiphospholipid antibody testing). To assess for appropriateness of testing, categories of data were collected including presence of other strong risk factors obviating the need to look for other causes, indicators for higher yield (age of patient, presence of family history of VTE, idiopathic nature of VTE), presence of factors that confound testing (such as therapeutic anticoagulation) and relevant follow up (appropriate repeat testing when necessary). We also collected basic patient demographics, VTE details and ordering physician/service details to evaluate under what circumstances testing may be ordered more frequently. RESULTS 134 charts of patients tested for thrombophilia were reviewed between 2007-2013 at UAH and RAH Hospitals. A total of 965 thrombophilia tests were done (see analysis table). 13.4% of the testing was ordered by hematologists, 23.1% by neurologists, 52.2% by other internists. Overall, all patients had tests performed inappropriately, lacked appropriate follow up or had uninterpretable results and none had documented counseling prior to thrombophilia testing. CONCLUSIONS Thrombophilia testing is frequently ordered inappropriately and not adequately followed up. Strategies to educate physicians on indications and limitations of testing are warranted. These strategies can help decrease over/under/misinterpretation of thrombophilia testing as well as result in significant savings to the health care system if testing can be reduced. Table 1. Demographics Sample Size Males Females Total 74 (55.22%) 60 (44.78%) 134 (100%) Age at time of testing (Yrs) Range 19-88 Average 48.7 Patients' Test Results Test Times Performed Abnormal Results APCR 134 (100%) 32 (23.8%) FVL genetic test 58 (43%) 21 (39%) PT20210 105 (77%) 4 (3.8%) Protein C 100 (74.1%) 8 (8%) Protein S 99 (73.3%) 16 (16.2%) AT levels 99 (73.3%) 19 (19.2%) Anticardiolipin Ab 117 (86.7%) 4 (3.4%) Lupus Anticoagulant 109 (81.3%) 10 (10.2%) Provoking Factors Patients with One or More Provoking Factors Major 10 7.4% Moderate 74 56% Minor 29 21.8% No Provoking Factors 49 36.8% Family History of VTE 12 8.9% Protein C and Protein S Testing Done During Acute VTE 64 64% Patient was on Warfarin 25 25% Number of Abnormal Test Results 24 16% Number of Repeated Abnormal Tests 0 0% AT Testing Total Tests Performed 99 73.3% Done During Acute VTE 62 63% Patient was on Therap. Heparin or LMWH 62 62.6% Number of Abnormal Test Results 19 19.2% Abnormal Tests Repeated? 7 37% Repeat Tests Showing Normal Results 3 57% APA Testing Tests were Repeated After 12 Weeks for Confirmation 11% Disclosures Wu: Leo Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

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Risk Factors for Ischaemic Stroke in an Omani Community

Sultan Qaboos University Medical Journal [SQUMJ] ◽

10.18295/squmj.4.2021.043 ◽

2021 ◽

Author(s):

Shyam Sundar Ganguly ◽

Arunodaya R. Gujjar ◽

Hasina Al Harthi ◽

Amal Al Hashmi ◽

Sanjay Jaju ◽

...

Keyword(s):

Risk Factors ◽

Logistic Regression ◽

Ischemic Stroke ◽

Family History ◽

High Density Lipoprotein ◽

Multivariate Logistic Regression Analysis ◽

Density Lipoprotein ◽

Case Control ◽

High Density ◽

History Of

Objectives: Stroke is recognized to be the third most common cause of mortality, with increasing incidence among developing countries. Recognition and control of risk factors is of prime importance in the prevention of stroke. We aimed to study the characteristics of ischemic stroke (IS) patients in Oman, and quantify its various risk factors using a case-control model. Methods: This study conducted from January 2012 to March 2013 included 255 adult Omani patients with IS admitted to two premier hospitals in Oman, compared to 255 age- and gender-matched controls. Demographic factors and frequency of various conventional risk factors were documented. Univariate and step-wise multivariate logistic regression analysis were performed to evaluate the risk factors associated for IS. Results: Of the 255 cases, 63% were males. The mean age was 62.2 ± 13.2 years. Most of the cases (89%) were above 45 years of age. Cardio-embolism(32%) was the commonest mechanism of IS. The stepwise multiple logistic regression model revealed that family history of stroke was the strongest independent risk factor with odds ratio (OR) of 10.10, followed by hypertension with OR of 5.17 and high-density lipoprotein with OR 3.34 (p< 0.01). Conclusions: Cardio-embolism was the predominant mechanism of IS in this study. Family history of stroke, hypertension and reduced high-density lipoprotein were the leading independent risk factors. Strong emphasis on screening for risk factors, control of hypertension and life-style modification for those with family history of stroke, would be expected to emerge as the major stroke-preventive measures in Oman. Keywords: Ischemic stroke; Risk factors; Case-control study; Oman.

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Abstract TP223: Characterizing Ischemic Stroke and Hemorrhagic Conversion in Infectious Endocarditis

Stroke ◽

10.1161/str.48.suppl_1.tp223 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Robert J Marquardt ◽

Sung-Min Cho ◽

Lucy Zhang ◽

Prateek Thatikunta ◽

Ken Uchino ◽

...

Keyword(s):

Risk Factors ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Risk Evaluation ◽

Mycotic Aneurysm ◽

Valve Surgery ◽

Preoperative Risk ◽

Tertiary Center ◽

History Of ◽

Cerebral Microhemorrhages

Introduction: Ischemic stroke is a common complication of infective endocarditis (IE) and can delay valve surgery. Identifying risk factors for acute ischemic stroke (AIS) and hemorrhagic conversion may help in perioperative risk assessment of these patients. Methods: Retrospective analysis was done on 116 consecutive patients with IE seen by stroke neurology at a tertiary center from January 2015 through July 2016. Clinical and radiographic characteristics were collected in a population whose initial evaluation was for acute stroke management or preoperative risk evaluation. Descriptive statistics were used to identify risk factors for AIS, defined as clinical or silent infarct, both with and without hemorrhagic conversion. Results: Among 116 patients with IE, AIS occurred in 82 (70.6%) with a median NIH Stroke Scale of 3 (interquartile range (IQR) 0-12) and a median MRI volume of 13.5mL (IQR 1.4-42mL). Of AIS patients, 25 (30%) had silent infarct, 6 (7%) had concurrent primary ICH without a clear ischemic component and 25 (30%) had hemorrhagic conversion. AIS was associated with remote stroke on imaging (OR 1.27), history of diabetes (OR 1.22), and &gt 1 vegetation on echocardiogram (OR 1.29), but not history of atrial fibrillation, microhemorrhages or mycotic aneurysm on imaging, MRI enhancing lesions, aortic versus mitral valve involvement, vegetation size, organism involved, IV drug abuse, or pre-admission antithrombotic use. Microhemorrhages on MRI susceptibility-weighted images occurred in 66 (80%) AIS patients, and was associated with hemorrhagic conversion (OR 1.35). Mycotic aneurysm was found in 4 patients with hemorrhagic conversion, but this was not significant (OR 1.0). A total of 48 AIS patients (58.5%) underwent valve surgery. Additional stroke occurred while awaiting surgery in 10 AIS patients (OR 1.20), 6 were new ischemic stroke and 4 were new ICH. Post-operatively there were 1 new AIS and 3 new ICH complications. Conclusion: The incidence of acute ischemic stroke in our population was 70.6%, with a third being silent infarcts. Hemorrhagic conversion occurred in 30% and was associated with cerebral microhemorrhages.

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Hereditary Deficiencies of Protein C or Protein S Confer Increased Risk of Arterial Thromboembolic Events at Young Age. Results from a Large Family Cohort Study

Blood ◽

10.1182/blood.v112.11.422.422 ◽

2008 ◽

Vol 112 (11) ◽

pp. 422-422

Author(s):

Bakhtawar Khan Mahmoodi ◽

Jan-Leendert P. Brouwer ◽

Nic J.G.M. Veeger ◽

Jan van der Meer

Keyword(s):

Risk Factors ◽

Protein C ◽

Protein S ◽

Thromboembolic Events ◽

Antithrombin Deficiency ◽

Increased Risk ◽

Atherosclerosis Risk ◽

History Of ◽

Arterial Thromboembolic Events ◽

Atherosclerosis Risk Factors

Abstract Introduction: Hereditary deficiencies of protein S, protein C or antithrombin are strong risk factors for venous thromboembolism (VTE). Whether these deficiencies are associated with arterial thromboembolism (ATE) and whether history of VTE in these subjects predisposes to subsequent ATE has yet to be determined. Methods: Based on pedigree analysis we enrolled a total 552 subjects (52% women; mean age, 46±17 years), belonging to 84 different kindreds, in this retrospective family-cohort study. Detailed information on previous episodes of VTE, ATE, anticoagulants use and atherosclerosis risk factors (i.e. diabetes, hypertension, hyperlipidemia, and smoking) were collected. In addition to the index deficiencies participants were also tested for other thrombophilic defects; including factor V Leiden, prothrombin G20210A, increased FVIII and lupus anticoagulants. Primary study outcome was objectively verified symptomatic ATE. As the assumption for proportional hazards for the final model was not met over the entire observation period, we opted for a piecewise Cox model with a cut off point set at 55 years of age. Results: Of 552 subjects (mean age±SD, 46±17 years; 52% women), 308 had either protein S (35%), protein C (39%) or antithrombin deficiency (26%). Age, atherosclerosis risk factors and other thrombophilic defects were similar (P>0.23) between deficient and non-deficient subjects. A total of 44 arterial thromboembolic events had occurred, corresponding to an overall annual incidences of 0.34% (95% CI, 0.23–0.49) in deficient and 0.17% (0.09–0.28) in non-deficient subjects, hazard ratio 2.3 (1.2–4.5; P=0.01). However, the risk hazards varied over lifetime; while risk of ATE conferred by these deficiencies was 5.4 (1.6–18.4; P=0.006) before age 55 years, it was 1.3 (0.6–2.9; P=0.51) thereafter. After adjusting for atherosclerosis risk factors and clustering of ATE within families, deficient subjects had 4.7-fold (1.5–14.2; P=0.007) higher risk of ATE before age 55 years, versus 1.1 (0.5–2.6; P=0.84) thereafter, compared to non-deficient family members. For separate deficiencies these were 4.6 (1.1 – 18.3), 6.9 (2.1 – 22.2) and 1.1 (0.1 – 10.9) in protein S-, protein C- and antithrombin-deficient subjects, respectively, before age 55 years. History of VTE was not related to subsequent ATE, hazard ratio 1.1 (0.5 – 2.2). Conclusions: Compared to non-deficient family members, subjects with protein S or protein C deficiencies but not antithrombin deficiency have an increased risk for ATE before age 55 years, independent of prior VTE. After age 55 years conventional atherosclerosis risk factors accounted for ATE. In thrombophilic families, deficiencies of protein S and protein C should be considered in atherothrombotic risk assessment before age 55 years.

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Lack of Association between Family History of Stroke and 1-year Outcomes after Acute Ischemic Stroke in Chinese

CNS Neuroscience & Therapeutics ◽

10.1111/cns.12164 ◽

2013 ◽

pp. n/a-n/a

Author(s):

Xin-Gao Wang ◽

Chun-Xue Wang ◽

Hua-Jun Yang ◽

An-Xin Wang ◽

Dong Li ◽

...

Keyword(s):

Ischemic Stroke ◽

Family History ◽

Acute Ischemic Stroke ◽

History Of

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Risk Factors and Long-term Follow-up of Patients with the Immune Type of Heparin-Induced Thrombocytopenia

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/107602960200800406 ◽

2002 ◽

Vol 8 (4) ◽

pp. 347-352 ◽

Cited By ~ 9

Author(s):

Edelgard Lindhoff-Last ◽

Britta Wenning ◽

Martina Stein ◽

Frank Gerdsen ◽

Rupert Bauersachs ◽

...

Keyword(s):

Risk Factors ◽

Factor Viii ◽

Protein C ◽

Protein S ◽

Factor Xii ◽

Factor V ◽

Heparin Induced Thrombocytopenia ◽

Long Term Follow Up

Dispositional risk factors for developing the immune-type of heparin-induced thrombocytopenia (HIT) are yet unclear. This article presents a long-term follow-up of patients with HIT to define possible risk factors that may increase the risk of HIT. The clinical course of acute HIT was analyzed retrospectively in 52 patients with HIT. Thirteen patients died;8 due to HIT. A follow-up investigation was performed in 28 of the remaining 39 patients 29 ± 12 months after the onset of HIT, including genotyping for the factor V G1691A- and the prothrombin G20210A-mutation, measurement of antithrombin, protein C, protein S, factor VIII, and factor XII activity as well as the concentration of antiphospholipid antibodies. The results were compared to an age- and sex-matched control group. New thromboembolic events and re-exposure to heparin were also documented. No difference between patients and controls was observed concerning the factor V Leiden mutation, the prothrombin mutation, factor XII, antithrombin, protein S, or protein C deficiency and antiphospholipid antibodies. Increased factor VIII activity was found in 16 of 21 HIT patients compared to 4 of 21 controls (p=0.0005). New thromboembolic events developed in 5 patients within 9 months after HIT. One patient had been re-exposed to heparin 9 months after acute HIT without any complications. Increased factor VIII activity was frequently observed in patients in whom HIT developed. Thromboembolic complications within the first months after onset of HIT occurred often.

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Risk factors including prothrombotic work up in young ischemic stroke Indian patients

International Journal of Advances in Medicine ◽

10.18203/2349-3933.ijam20201029 ◽

2020 ◽

Vol 7 (4) ◽

pp. 547

Author(s):

Amit Sreen ◽

Prafull Sharma ◽

Vivek Guleria ◽

Niket Verma

Keyword(s):

Risk Factors ◽

Ischemic Stroke ◽

Protein C ◽

Tertiary Care ◽

Protein S ◽

Protein C Deficiency ◽

Factor V Leiden Mutation ◽

Major Health Problem ◽

Work Up ◽

Stroke In Young

Background: Stroke in young poses a major health problem. Various Indian studies have shown the incidence of stroke to be 10-15%. Cerebral venous thrombosis and rheumatic heart disease are the leading causes of stroke in the young in India. Thrombophilic factors have been implicated in 4-8% of the young strokes worldwide. Protein C deficiency is the most common thrombophilia marker followed by a deficiency of protein S, Factor V Leiden mutation, and antithrombin (AT) deficiency. Aims and objectives was the study of stroke in young is important for various reasons. The etiology and risk factors are more diverse and different as compared to the elderly. Therefore, these may indicate separate therapeutic approaches. The aim is to study the profile of ischemic stroke cases among the young.Methods: The study was carried out at a tertiary care defence hospital between December 2018 to December 2019. All cases of fresh ischemic stroke who were more than 15 and less than 45 years of age were included. Following clinical evaluation, patients underwent complete haemogram, blood sugar levels, lipid profile and other metabolic parameters. All patients were subjected to chest radiography, 12 lead ECG, and 2D echocardiography, Non-contrast CT head and MRI brain. Prothrombotic work up was also done.Results: A total of 41 patients (12.69%) presented with ischemic stroke before 45 years of age. Out of these 10 (24%) were females and 31 (76%) were male. None of the women smoked or consumed alcohol. Among the males, 19 (47%) smoked more than 10 cigarettes or bidis per day and 9 (22%) were moderate-to-heavy drinkers of alcohol. Hypertension was present in 7 (18%) and diabetes mellitus in 3 (7%) patients. Serum cholesterol was elevated in 7 (18%) patients and triglycerides in 17 (42%). Protein S deficiency was found in 28.8% patients, while protein C deficiency was detected in 21% patients and antithrombin III deficiency in 12% patients.Conclusions: Although traditional risk factors, such as hypertension, diabetes, and smoking, are associated with stroke in both elderly and young, this study shows that other modifiable risk factors such as alcohol consumption were also prevalent. The most common etiological cause was found to be venous infarction followed by cardio embolic cause. Deficiency of Protein S was the most common prothrombotic defect followed by deficiency of Protein C.

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Risk Factors, Clinical Manifestations, Treatment Duration and Outcomes in Carriers of Severe Inherited Thrombophilias

Blood ◽

10.1182/blood-2019-132248 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 3657-3657

Author(s):

Ivan Bascon ◽

Paul J Christos ◽

Maria Teresa De Sancho

Keyword(s):

Risk Factors ◽

Family History ◽

Protein C ◽

Thrombotic Event ◽

Clinical Manifestations ◽

Double Heterozygote ◽

Gain Of Function ◽

Inherited Thrombophilia ◽

History Of ◽

Double Heterozygosity

Background Severe Inherited thrombophilia comprisses deficiencies of natural anticoagulants (antithrombin (AT), protein C (PC), and protein S (PS), and homozygosity for factor V Leiden (FVL) or prothrombin gene mutation (PGM) or double heterozygosity or other combined thrombophilia. Carriers of AT, PC and PS have a high risk of thrombosis starting at a young age, usually several members of the same family are affected and thrombosis may occur at unusual locations. Conversely homozygotes for either FVL, PGM or double heterozygotes may not have a family history of thrombosis and the first thrombotic event may present later on life. It is also unclear what is the duration and type of anticoagulation and long-term outcomes of these carriers. The purpose of this study was to compare risk factors, clinical manifestations, type and duration of anticoagulation and clinical outcomes between carriers of anticoagulant deficiencies and those with gain of function mutations (homozygosity or double heterozygosity for FVL and PGM). Methods Retrospective evaluation of electronic medical records of patients with severe inherited thrombophilia referred to the Center for Blood Disorders at Weill Cornell Medicine-New York Presbyterian Hospital between January 2009 and June 2019. Severe deficiencies of AT, PC and PS were defined and (AT ≤ 60%, PC ≤ 50% and PS ≤ 40% (2). Patients without confirmatory laboratory results for the anticoagulant deficiencies were excluded from the study. We collected demographic data, risk factors for thrombosis, family history, type of thrombotic events, pregnancy complications in females, type and duration of anticoagulant and outcomes. Statistical analysis was performed using descriptive statistics and chi-square test was applied for comparison of variables between anticoagulant deficiency carriers and gain of function mutation carriers. Results Of a total of 107 patients identified,17 were excluded due to absence of confirmatory results. A total of 90 patients were analyzed; 70 (78%) females; mean age and range 44 (22- 82). There were 34 (38%)patients with anticoagulant deficiencies (10 AT, 6 PC and 18 PS) and 56 (62%) homozygotes for FVL, PGM or double heterozygote. Of those, 23 (39%) homozygote for FVL with one also heterozygote for the PGM, 2 (3.6%) homozygote PGM and 31(55.4%) double heterozygote. Overall risk factors for thrombosis were similar in both groups. There were no identified thrombosis risk factors in 12 and 19 patients in the anticoagulant deficiency and gain of function mutation respectively. The most common type of clinical presentation in both groups was deep vein thrombosis and pulmonary embolism. A positive family history of either thrombosis of thrombophilia in a first degree family member was equal in both groups. Likewise age less than 40 at first thrombotic event was similar. The most frequent anticoagulant prescribed in the patients with anticoagulant deficiency was a direct oral anticoagulant in 26.%% and vitamin K antagonists 22.3% in the ones with gain of function mutation. More patients with anticoagulant deficiencies remain on anticoagulation for more than 1 year than the ones with a gain of function mutation (88.5% vs 64%) and had more recurrent thrombotic events (20.6% vs.5.4%). Within the 70 female patients, 5 (7%) had first trimester pregnancy loss and 14 (20%) had multiple pregnancy losses. Conclusions: Our results suggest that patients with severe inherited antithrombin, protein C and S deficiencies have worse outcomes despite longer duration of anticoagulation than patients homozygote or double heterozygote for gain of function mutations. Disclosures De Sancho: Apellis Pharmaceuticals: Other: Advisory Board; BPL: Other: Advisory Board.

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