Hypercoagulability in ACTH-Dependent Cushing Syndrome

Abstract Introduction: ACTH-dependent Cushing syndrome (CS) is associated with hypercoagulability; however, the incidence and timing of thrombosis during evaluation and management of CS is unclear. Objective: To evaluate the incidence and timing of thrombotic events in patients with ACTH-dependent CS following diagnosis and management. Methods: We performed a retrospective, longitudinal study of patients with ACTH-dependent CS seen at Stanford University Health Care from 1998 to 2020. Thrombotic events — deep vein thrombosis (DVT), pulmonary embolism (PE), cerebral vascular accident (CVA), and myocardial infarction (MI) — were recorded between diagnosis and 12 months following therapeutic intervention. Results: Of 108 patients with ACTH-dependent CS, 97 (89.8%) were women, and the mean age at diagnosis was 43.0 years (± 15.7 years). Sixty-eight (63%) patients had hypertension, 38 (35.2%) had diabetes mellitus, and 11 (10.2%) were active smokers. Of the 108 subjects, 97 (89.8%) had Cushing Disease (CD) and 11 (10.2%) had ectopic CS. Of the 97 patients with CD, 38 (39.2%) underwent inferior petrosal sinus sampling (IPSS), 59 (60.8%) underwent transsphenoidal surgery (TSS), 19 required repeat TSS (19.6%), and 15 underwent TSS and bilateral adrenalectomy (BAL) (15.4%). Of the 11 patients with ectopic CS, 3 (27.2%) underwent IPSS, 6 (54.5%) underwent BAL, and 1 (9.1%) underwent TSS and BAL. There were 10 thrombotic events among 7 (7.2%) CD patients, but no thrombotic events among ectopic CS patients. Of the thrombotic events, there were 7 (70%) DVT/PE, 2 (20%) CVA, and 1 (10%) cortical vein thrombosis. Six (60%) occurred within 30 days after TSS (range 3-25 days), 2 (20%) between 31 days and 1 year after TSS (range 59-165 days), 1 (10%) 26 days after IPSS but prior to TSS, and 1 (10%) in a patient who did not undergo IPSS or surgery. No thrombotic events were noted after BAL. Of the 8 postoperative thrombotic events, 5 (62.5%) occurred while patients received supraphysiologic glucocorticoid replacement (defined as >25mg hydrocortisone or equivalent daily) after curative surgery, 1 (12.5%) occurred after a patient was tapered to physiologic glucocorticoid replacement, and 2 (25%) occurred in patients who had persistent disease despite surgery. The degree of hypercortisolism at baseline was not associated with risk of thrombotic events. Conclusions: In this retrospective study, 6.5% of ACTH-dependent CS patients had a thrombotic event, all in patients with CD. The majority had venous thromboembolism with DVT/PE, and the highest incidence occurred up to 30 days after surgery. The degree of hypercortisolism at baseline did not correlate with subsequent thrombotic events. Therefore, it is important to monitor all patients with ACTH-dependent CS following surgical intervention for venous thromboembolism.

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Incidence and Risk Factors of Venous Thromboembolism After Orthopaedic Foot and Ankle Surgery

Foot & Ankle Specialist ◽

10.1177/1938640017704944 ◽

2017 ◽

Vol 10 (5) ◽

pp. 449-454 ◽

Cited By ~ 12

Author(s):

Jamal Ahmad ◽

Mary-Katherine Lynch ◽

Mitchell Maltenfort

Keyword(s):

Venous Thromboembolism ◽

Tendon Repair ◽

Significant Degree ◽

Fracture Repair ◽

Medical Comorbidities ◽

Vein Thrombosis ◽

Ankle Ligament ◽

Ankle Surgery ◽

The Mean ◽

Deep Vein

Background. This study examines the incidence and risk of postoperative symptomatic venous thromboembolism (VTE) after orthopaedic foot/ankle surgery. Materials. Patients that received foot/ankle surgery between 2006 and 2016 were reviewed. Inclusion criteria were surgical patients that were without coagulopathy, previous VTE, and/or using anticoagulation medications including aspirin. Age, sex, body mass index, medical comorbidities, and surgical diagnosis and procedure(s) were noted. Records were reviewed to see who developed a symptomatic VTE within 90 days from surgery. Results. This study involved 2774 patients that received foot/ankle surgery between 2006 and 2016. Of them, 22 (0.79%) developed a VTE within 90 days from surgery. The mean age of these patients was 49.5 years. Twelve patients were male and 10 were female. Sixteen patients were obese and 6 were nonobese. Postoperative VTEs were 14 infrapopliteal deep vein thrombosis (DVT), 1 suprapopliteal DVT, and 7 pulmonary emboli. The most common surgeries involved were ankle fracture repair in 8 (0.29%), Achilles tendon repair in 2 (0.07%), ankle ligament reconstruction in 2, and hammer-toe correction in 2 patients. Obesity was predictive of a postoperative VTE to a statistically significant degree (P = .04). Age, sex, medical comorbidities, diagnosis, and type of surgery were not significantly prognostic for a postsurgical VTE (P ≥ .05). Discussion. The incidence of VTE after foot/ankle surgery is low. However, obese patients are at significantly higher risk for VTE after such procedures. Clinical Relevance. These findings are important when educating patients as to their risks of developing a VTE after orthopaedic foot/ankle surgery. Levels of Evidence: Level III: Retrospective cohort study

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Reduced Calf Muscle Pump Function Is a Risk Factor for Venous Thromboembolism and Mortality

Blood ◽

10.1182/blood-2020-139385 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 6-7

Author(s):

Damon E. Houghton ◽

Aneel A. Ashrani ◽

Ramila Mehta ◽

David O. Hodge ◽

David Liedl ◽

...

Keyword(s):

Deep Vein Thrombosis ◽

Venous Thromboembolism ◽

Calf Muscle ◽

Olmsted County ◽

Pump Function ◽

Muscle Pump ◽

Vein Thrombosis ◽

Calf Muscle Pump ◽

The Mean ◽

Deep Vein

Background: Venous return from the lower extremities is pumped upwards to the right side of the heart in a process that is facilitated by one-way valves and the venous muscle pump, of which the calf muscle pump is a major contributor1-3. Venous plethysmography can quantitatively assess calf pump function (CPF). The association between the CPF and venous thromboembolism (VTE) has not been investigated. Methods: Venous plethysmography (VP) data (strain gauge or air plethysmography) from the Mayo Clinic Vascular Lab database (1998-2015) of CPF (bilaterally reduced, unilaterally reduced, and bilateral normal) were examined in Olmsted County Residents. The Rochester Epidemiology Project (REP) captures the population of Olmsted County and contains demographic information, medical diagnoses, hospital admissions, and surgical procedures as well as validated VTE events and death. Patients with signs of obstructed outflow in either extremity on the venous plethysmography (a possible sign of acute or chronic deep vein thrombosis) study were excluded. Patients with a history of VTE diagnosed before the physiologic study were also excluded. If more than one measurement of calf muscle pump function was performed, only the first measurement was used. The primary outcome was a composite of any VTE, including proximal and distal deep vein thrombosis (DVT) and pulmonary embolism (PE). Results: 1703 Olmsted County residents had venous plethysmography studies performed. MN research authorization was denied in 64 patients and 107 were excluded for any documented VTE preceding index VP study. 1532 patients with recorded CPF (28% air and 72% strain gauge plethysmography) were studied: 591 (38.5%) had normal CPF, 353 (23.0%) had unilateral reduced CPF (rCPF), and 588 (38.3%) had bilateral rCPF. The mean age was 64.4 (SD 18.4), 68.9% were female, and the mean BMI was 29.5 (SD 6.4). Any VTE occurred in 87 patients (5.7%) after a mean follow up of 10.9 years (range 0-22.0 years). Isolated lower extremity DVT (excluding concurrent PE) occurred in 49 patients and PE+/-DVT occurred in 38 patients. Death occurred in 352 patients (23%). Bilateral rCPF compared to bilateral normal CPF was associated with VTE (p=0.007), DVT only (p=0.02) and death (p<0.001) but not PE+/-DVT (p=0.13). Unilateral rCPF compared to bilateral normal CPF was not associated with VTE, but was associated with death (p<0.001). Kaplan-Meier curves for VTE and death are shown in Figure 1. The hazard ratio for bilateral rCPF compared to bilateral normal CPF for VTE was 2.0 (95% CI 1.2-3.4) and for DVT only was 2.2 (95% CI 1.1-4.2). A sensitivity analysis for the main outcome of VTE did not show significant interaction based on the type of plethysmography (strain vs. air), by age stratified at 65 years, sex, or BMI stratified at 30 (p>0.1 for each comparison). Conclusion: In this population-based study of Olmsted County residents with no prior VTE, rCPF function as measured by venous plethysmography is associated with increased risk for VTE, particularly lower extremity proximal DVT. More research is required to understand what additional measures of venous physiology influence these findings and whether CPF could be used in VTE risk stratification. Disclosures No relevant conflicts of interest to declare.

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A study on the effectiveness of wells criteria for diagnosing deep vein thrombosis: a prospective observational study

International Surgery Journal ◽

10.18203/2349-2902.isj20210365 ◽

2021 ◽

Vol 8 (2) ◽

pp. 569

Author(s):

Dhanaraj Palanisamy ◽

Akshay Omkumar

Keyword(s):

Deep Vein Thrombosis ◽

Single Case ◽

Post Partum ◽

Clinical Signs ◽

Study Group ◽

Cortical Vein ◽

Vein Thrombosis ◽

Cortical Vein Thrombosis ◽

Wells Score ◽

Deep Vein

Background: Wells score which takes into account various aspects in the history as well as various clinical signs which can help the clinician to arrive at a diagnosis of deep vein thrombosis (DVT). This helps to save time and money that is wasted in doing many unnecessary investigations. Aim of the study was to test the application of the Wells score in our clinical set up and to see how effectively we can diagnose DVT.Methods: This was a prospective diagnostic validation study of the wells rule for DVT in our setup, ultrasound (USG) being the gold standard comparison and will be conducted over a duration of 12 months. Wells score for each patient was calculated and the results were evaluated.Results: Among the 50 cases suspected DVT, the wells score was able to predict DVT in 46 of the cases thus proving to be a very efficient diagnostic indicator. The average wells score among the various cases was 4/8. Complications noted in the study group were 2 cases of cortical vein thrombosis in the post-partum period which fully recovered. Mortality rate in the study group was 4.3% in which a single case of diagnosed myocardial infarction died of heart failure.Conclusions: Wells score is indeed a very good predictive criteria for DVT and can be applied with ease as it required only clinical assessment and thus avoids unnecessary delays in waiting for scans thereby allowing us to start anticoagulants as early as possible.

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Cortical Vein Thrombosis after Infliximab Treatment for Crohn’s Disease

Neurology International ◽

10.3390/neurolint13010011 ◽

2021 ◽

Vol 13 (1) ◽

pp. 120-124

Author(s):

Saeed Razmeh ◽

Nafiseh Niknam ◽

Negar Sadat Rabbani ◽

Shekoofeh Nikoee ◽

Fatemeh Vafa Pour ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Pulmonary Thromboembolism ◽

Infliximab Treatment ◽

Cortical Vein ◽

Vein Thrombosis ◽

First Case ◽

Cortical Vein Thrombosis ◽

Inflammatory Bowel ◽

Deep Vein

Inflammatory bowel disease (IBD) including ulcerative colitis and Crohn’s disease puts patients at high risk of thromboembolism accidents. These patients may take infliximab for active and fistulating Crohn’s disease, which can also increase the risk of thrombosis. Deep vein thrombosis (DVT) and pulmonary thromboembolism (PTE) are more common among these patients, but cerebrovascular, mesenteric, portal and retinal veins can also be affected. In this paper, we report a case of isolated right Labbe vein thrombosis after infliximab therapy for Crohn’s disease. To the best of our knowledge, our patient is the first case report of isolated cortical vein thrombosis following administration of rituximab for Crohn’s disease.

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Serological Parameters and Vascular Investigation for a Better Assessment in DVT during Pregnancy—A Systematic Review

Medicina ◽

10.3390/medicina57020160 ◽

2021 ◽

Vol 57 (2) ◽

pp. 160

Author(s):

Catalina Filip ◽

Demetra Gabriela Socolov ◽

Elena Albu ◽

Cristiana Filip ◽

Roxana Serban ◽

...

Keyword(s):

Systematic Review ◽

Deep Vein Thrombosis ◽

Venous Thromboembolism ◽

Correct Diagnosis ◽

Thrombotic Event ◽

Vein Thrombosis ◽

Major Consequence ◽

Life Threatening ◽

The Right ◽

Deep Vein

Pregnancy and the postpartum period represent a condition characterized by a thrombotic predisposition. The majority of pregnant women do not face acute or severe thrombotic events. In general, mild inconveniences such as leg swelling or moderately painful thrombotic events (phlebitis) are encountered. However, when pregnancy is associated with inherited or acquired deficits that affect homeostasis, the risk of acute or even life-threatening events can increase significantly. The major consequence is the loss of the fetus or the venous thromboembolism that endangers the mother’s life. Venous thromboembolism is caused by deep vein thrombosis, therefore timely detection and especially the assessment of the extent of the thrombotic event are crucial. In this paper we have summarized the most important paraclinical investigations. The study emphasizes the importance of selecting the methods of investigation. The right choice allows establishing a correct diagnosis and individualizing the treatment.

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Lupus Anticoagulant Testing in Patients Receiving Rivaroxaban or Apixaban for the Treatment of Venous Thromboembolism

Blood ◽

10.1182/blood.v128.22.5017.5017 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5017-5017 ◽

Cited By ~ 1

Author(s):

Matthew R. Kovacs ◽

Alejandro Lazo-Langner ◽

Martha L Louzada ◽

Michael J. Kovacs

Keyword(s):

Venous Thromboembolism ◽

Lupus Anticoagulant ◽

Research Funding ◽

Vein Thrombosis ◽

Liquid Chromatography Tandem Mass ◽

Valid Assessment ◽

Technical Issues ◽

The Mean ◽

Deep Vein ◽

Current Guidelines

Abstract Background. Lupus Anticoagulant (LA) testing is often performed in order to determine the cause of idiopathic venous thromboembolism (VTE) as well as the duration of therapy. The timing of the testing is often problematic. Acutely, many patients have received LMWH which often will interfere with test results. LA testing in patients on warfarin is technically feasible and current guidelines have established procedures for this situation. In contrast direct anti-Xa inhibitors such as apixaban and rivaroxaban can cause false positive results if residual anti-Xa inhibition is present. In general, prior to performing a thrombophilia screen, anticoagulants must be held in order to produce valid results. The duration of this varies with different anticoagulants. Some groups have advised that apixaban and rivaroxaban should be held for 2-3 days prior to testing. This overcomes the half-life of both agents. However, to date there have not been adequate studies to validate this approach, and no standardized approach has been proposed. At our centre we require patients to withhold apixaban or rivaroxaban on the day prior to and the day of LA testing. We aimed to determine the adequacy of this approach. Methods. We reviewed consecutive patients with VTE treated with rivaroxaban or apixaban and who required LA screening. . LA testing was requested at least 3 months after the initial VTE diagnosis. Patients were asked to hold the anticoagulant the day prior to and the day of LA testing (last dose taken at least 48 hours prior to testing). Plasma was collected in 3.2% citrate tubes and LA testing was done using dilute Russell viper's venom time and LA-sensitive activated partial thromboplastin time, according to the guidelines of the International Society on Thrombosis and Haemostasis. Plasma aliquots were frozen at -20 Celsius for further testing and apixaban or rivaroxaban plasma levels were measured by liquid chromatography-tandem mass spectrometry. Results. We included 21 patients (13 women). The mean age at VTE diagnosis was 57 years. Twelve patients had a pulmonary embolism (PE), 10 deep vein thrombosis (DVT), and 1 both a PE and DVT. Sixteen (76.2%) of the 21 patients received rivaroxaban, the rest apixaban. The mean apixaban level was 17.3 ng/ml (range 11.4 to 28.9). The mean rivaroxaban level was 11.7 ng/ml (range 8 to 27.8). All of these levels were consistent with being below trough levels for acute VTE treatment. All patients were negative for LA screening and there were no technical issues with performing the LA tests. Conclusion. Our results suggest that holding rivaroxaban or apixaban both the day prior to and the day of testing allows for a valid assessment of LA. This is supported by the low measured levels of both rivaroxaban and apixaban and the lack of technical issues with the LA testing. Disclosures Lazo-Langner: Bayer: Honoraria; Pfizer: Honoraria; Daiichi Sankyo: Research Funding. Louzada:Pfizer: Honoraria; Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Bayer: Honoraria. Kovacs:Daiichi Sankyo Pharma: Research Funding; Bayer: Honoraria, Research Funding; LEO Pharma: Honoraria; Pfizer: Honoraria, Research Funding.

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Features of Thrombi and Diagnostic Accuracy of Impedance Plethysmography in Symptomatic and Asymptomatic Deep Vein Thrombosis

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649563 ◽

1993 ◽

Vol 70 (02) ◽

pp. 266-269 ◽

Cited By ~ 21

Author(s):

Giancarlo Agnelli ◽

Benilde Cosmi ◽

Stefano Radicchia ◽

Franca Veschi ◽

Enrico Boschetti ◽

...

Keyword(s):

Deep Vein Thrombosis ◽

Diagnostic Accuracy ◽

High Sensitivity ◽

Impedance Plethysmography ◽

Surveillance Programme ◽

Vein Thrombosis ◽

Asymptomatic Patients ◽

High Prevalence ◽

The Mean ◽

Deep Vein

SummaryImpedance plethysmography (IPG) has high sensitivity and specificity in patients with symptomatic deep vein thrombosis (DVT) while it fails to detect asymptomatic DVT. The aim of this study was to determine whether the features of thrombi such as location, size and occlusiveness could explain the different accuracy of IPG in symptomatic and asymptomatic DVT patients. One-hundred and seventeen consecutive outpatients with a clinical suspicion of DVT and 246 consecutive patients undergoing hip surgery were admitted to the study. In symptomatic patients IPG was performed on the day of referral, followed by venography, while in asymptomatic patients IPG was performed as a surveillance programme, followed by bilateral venography.A venography proved DVT was observed in 37% of the symptomatic patients and 34% of the asymptomatic limbs. A significantly higher proportion of proximal DVTs was found in symptomatic patients than in asymptomatic patients (78% vs 46%; p = 0.001). The mean Marder score, taken as an index of thrombus size, was significantly higher in symptomatic patients than in asymptomatic patients (19.0 vs 9.6; p = 0.0001). A significantly higher proportion of occlusive DVTs was observed in symptomatic than in asymptomatic patients (69% vs 36%; p = 0.001).We conclude that the unsatisfactory diagnostic accuracy of IPG in asymptomatic DVT is due to the high prevalence of distal, small and non occlusive thrombi. Such thrombi are unlikely to cause a critical obstruction of the venous outflow and therefore to produce a positive IPG.

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Pre-operative Plasma Levels of Thrombin-Antithrombin III Complexes Correlate with the Development of Venous Thrombosis after Major Hip or Knee Surgery

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649782 ◽

1995 ◽

Vol 74 (02) ◽

pp. 602-605 ◽

Cited By ~ 18

Author(s):

Jeffrey S Ginsberg ◽

Patrick Brill-Edwards ◽

Akbar Panju ◽

Ameen Patel ◽

Joanne McGinnis ◽

...

Keyword(s):

Antithrombin Iii ◽

Tertiary Care ◽

Knee Surgery ◽

Referral Centre ◽

Study Objective ◽

Cut Points ◽

Vein Thrombosis ◽

Major Orthopedic Surgery ◽

The Mean ◽

Deep Vein

SummaryStudy objective. To determine whether levels of thrombin-antithrombin III (TAT) in plasma, taken two weeks pre-operatively, predict the development of deep vein thrombosis (DVT) in patients undergoing major hip or knee surgery.Design. Prospective cohort.Setting. Tertiary-care referral centre, university-affiliated hospital.Patients. Ninety eight consecutive patients undergoing elective hip or knee surgery.Intervention. All eligible consenting patients were seen in a preoperative clinic two weeks prior to surgery and had blood taken for measurement of plasma TAT level. After surgery, they received a combination of unfractionated heparin 5000 Units 12-hourly subcutaneously, and antiembolism stockings (TEDS), as prophylaxis against DVT. Contrast venography was performed prior to discharge, and according to the results, patients were classified as having proximal (popliteal and/or more proximal) DVT (n = 12), calf DVT (n = 7) or no DVT (n = 79).Measurements and Results. The mean TAT level was significantly higher in patients who developed DVT (5.7 μg/l) than in those who did not (4.1 μg/l), p = 0.035. Using cut-points of 3.5 and 5.5 μg/l for the TAT level, patients could be categorized as high, intermediate, and low risk for the development of DVT. The proportion of patients with TAT levels of ≥3.5μg/l who developed calf or proximal DVT was significantly higher than the proportion of patients with TAT levels of <3.5 μg/l who developed calf or proximal DVT (p = 0.02). The proportion of patients with TAT levels >5.5 μg/l who developed proximal DVT was significantly higher than the proportion of patients with TAT levels of ≤5.5 μg/l who developed proximal DVT (p = 0.03).Conclusions. This study demonstrates that pre-operative TAT levels correlate with the risk of developing DVT after major orthopedic surgery. Further studies are needed to determine the reason(s) for this observation and whether rational recommendations about prophylaxis and screening for DVT can be made based on the results of a pre-operative TAT level.

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Multimodal diagnosis of cortical vein thrombosis

Aktuelle Neurologie ◽

10.1055/s-2007-987497 ◽

2007 ◽

Vol 34 (S 2) ◽

Author(s):

J Linn ◽

T Pfefferkorn ◽

S Michl ◽

M Wiesmann ◽

S Hartz ◽

...

Keyword(s):

Cortical Vein ◽

Vein Thrombosis ◽

Cortical Vein Thrombosis

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Cerebellar venous thrombosis mimicking a cerebellar tumor due to polycythemia vera: a case report

BMC Neurology ◽

10.1186/s12883-021-02261-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Hongfeng Wen ◽

Di Jin ◽

Yu Chen ◽

Bin Cui ◽

Tianyi Xiao

Keyword(s):

Venous Thrombosis ◽

Polycythemia Vera ◽

Delayed Diagnosis ◽

Janus Kinase ◽

Cerebellar Hemisphere ◽

Cerebellar Tumor ◽

Cortical Vein ◽

Vein Thrombosis ◽

Cortical Vein Thrombosis ◽

V617f Mutation

Abstract Background Cerebral venous thrombosis (CVT) occurs rarely in the general population and is frequently associated with confused clinical findings and delayed diagnosis. Isolated cerebellar cortical vein thrombosis is a very rare phenomenon. Case presentation This report describes a case with CVT, which is manifested as space-occupying lesions of the cerebellar hemisphere and mimics a cerebellar tumor at the beginning. The diagnosis of CVT was finalized given the laboratory and brain biopsy findings. The etiology may be related to polycythemia vera with Janus Kinase 2 V617F mutation. Conclusion Isolated cerebellar vein thrombosis should be considered when swelling and enhancing cerebellar lesions are detected. Polycythemia vera, especially with a positive JAK2 V617F mutation, may be a rare risk factor for CVT.

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