Victoria Vardell, MD

BACKGROUND

There are 5 germline mutations that lead to hypercoagulability in the general population including: Factor V Leiden (FVL), Prothrombin G20210A (F2A), Protein C Deficiency (PCD), Protein S Deficiency (PSD), and Antithrombin Deficiency (ATD). Typical guidance is to defer testing, as it is thought not to change management.

CASE REPORT

We present a case of a patient who was found to be compound heterozygous mutations for FVL and F2A, who presented with two episodes of arterial thromboembolism resulting in cerebrovascular accident (CVA). A 63-year-old male with past medical history of hypertension, a CVA four years prior, and medication non-compliance presents with new onset left sided hemiparesis after an episode of convulsions. MRI and CT imaging of the head revealed ischemic CVA secondary to thromboembolism in the right posterior cerebral artery’s (PCA), P1 branch. Following administration of tissue plasminogen activator (tPA) he had rapid symptom improvement. This second ischemic CVA prompted a workup which was notable for: negative echocardiogram, negative 30-day cardiac monitor, CT chest negative for malignancy, no significant vascular findings, negative for antiphospholipid syndrome, but genetic testing revealed the patient to be heterozygous for FVL and F2A mutations. He was started on apixaban 5 mg twice daily for ongoing secondary prevention. Though medication compliance continues to be difficult, after being placed on direct anticoagulant (DOAC), he has not had recurrent venous or arterial thrombotic events. A small case series found double heterozygosity for FVL and F2A further increases the risk of venous thromboembolism up to 17% or more in a lifetime.

CONCLUSIONS

Although current recommendations advocate against testing for specific mutations in most cases as it is likely not to change management1, this case suggests that it may be of some benefit in patients that have a workup that does not yield a clear etiology, especially in cryptogenic stroke which is typically managed with aspirin rather than direct oral anticoagulant.

BACKGROUND

There are 5 germline mutations that lead to hypercoagulability in the general population including: Factor V Leiden (FVL), Prothrombin G20210A (F2A), Protein C Deficiency (PCD), Protein S Deficiency (PSD), and Antithrombin Deficiency (ATD). Typical guidance is to defer testing, as it is thought not to change management.

CASE REPORT

We present a case of a patient who was found to be compound heterozygous mutations for FVL and F2A, who presented with two episodes of arterial thromboembolism resulting in cerebrovascular accident (CVA). A 63-year-old male with past medical history of hypertension, a CVA four years prior, and medication non-compliance presents with new onset left sided hemiparesis after an episode of convulsions. MRI and CT imaging of the head revealed ischemic CVA secondary to thromboembolism in the right posterior cerebral artery’s (PCA), P1 branch. Following administration of tissue plasminogen activator (tPA) he had rapid symptom improvement. This second ischemic CVA prompted a workup which was notable for: negative echocardiogram, negative 30-day cardiac monitor, CT chest negative for malignancy, no significant vascular findings, negative for antiphospholipid syndrome, but genetic testing revealed the patient to be heterozygous for FVL and F2A mutations. He was started on apixaban 5 mg twice daily for ongoing secondary prevention. Though medication compliance continues to be difficult, after being placed on direct anticoagulant (DOAC), he has not had recurrent venous or arterial thrombotic events. A small case series found double heterozygosity for FVL and F2A further increases the risk of venous thromboembolism up to 17% or more in a lifetime.

CONCLUSIONS

Although current recommendations advocate against testing for specific mutations in most cases as it is likely not to change management1, this case suggests that it may be of some benefit in patients that have a workup that does not yield a clear etiology, especially in cryptogenic stroke which is typically managed with aspirin rather than direct oral anticoagulant.

BACKGROUND

There are 5 germline mutations that lead to hypercoagulability in the general population including: Factor V Leiden (FVL), Prothrombin G20210A (F2A), Protein C Deficiency (PCD), Protein S Deficiency (PSD), and Antithrombin Deficiency (ATD). Typical guidance is to defer testing, as it is thought not to change management.

CASE REPORT

We present a case of a patient who was found to be compound heterozygous mutations for FVL and F2A, who presented with two episodes of arterial thromboembolism resulting in cerebrovascular accident (CVA). A 63-year-old male with past medical history of hypertension, a CVA four years prior, and medication non-compliance presents with new onset left sided hemiparesis after an episode of convulsions. MRI and CT imaging of the head revealed ischemic CVA secondary to thromboembolism in the right posterior cerebral artery’s (PCA), P1 branch. Following administration of tissue plasminogen activator (tPA) he had rapid symptom improvement. This second ischemic CVA prompted a workup which was notable for: negative echocardiogram, negative 30-day cardiac monitor, CT chest negative for malignancy, no significant vascular findings, negative for antiphospholipid syndrome, but genetic testing revealed the patient to be heterozygous for FVL and F2A mutations. He was started on apixaban 5 mg twice daily for ongoing secondary prevention. Though medication compliance continues to be difficult, after being placed on direct anticoagulant (DOAC), he has not had recurrent venous or arterial thrombotic events. A small case series found double heterozygosity for FVL and F2A further increases the risk of venous thromboembolism up to 17% or more in a lifetime.

CONCLUSIONS

Although current recommendations advocate against testing for specific mutations in most cases as it is likely not to change management1, this case suggests that it may be of some benefit in patients that have a workup that does not yield a clear etiology, especially in cryptogenic stroke which is typically managed with aspirin rather than direct oral anticoagulant.

BACKGROUND

Ewing sarcoma (EWS) is a malignancy which primarily arises in adolescence and has been studied extensively in this population. Much less is www.mdedge.com/fedprac/avaho SEPTEMBER 2023 • S23 known about the rare patient cohort over the age of 40 at diagnosis. In this study, we describe the survival outcomes and clinical characteristics of this population.

METHODS

This retrospective cohort study utilized the National Cancer Database (NCDB) to identify 4600 patients diagnosed between 2004 through 2019. Of these patients, 4058 were under the age of 40 and 542 were over 40. Multivariate Cox regression models and Kaplan- Meier curves were used to estimate survival from diagnosis to death between age groups. Chi-square tests were used to compare demographic and socioeconomic patient characteristics. IBM SPSS version 27.0 was used. p<0.05 was used to indicate statistical significance.

RESULTS

EWS patients older than 40 experienced worse survival outcomes compared to patients under the age of 40. 5-year survival was 43.5% for older patients vs. 64.5% for younger patients (p<0.05). A multivariate Cox proportional hazards model showed that age was independently associated with inferior survival. (HR 2.23; p<0.05). EWS patients over the age of 40 were more likely to have tumors originating from the vertebral column (16.2% vs. 9.6%; p<0.05), cranium (5.5% vs. 4.7%; p<0.05), and had a higher rate of axial tumors (43.3% vs. 32.4%; p<0.05) compared to patients under 40. Additionally, patients older than 40 experienced a significantly longer delay between the date of diagnosis and initiation of systemic treatment (29.85 days vs. 19.37 days; p<0.05). Despite presenting with larger tumors , older patients were less likely to undergo a surgical procedure of the primary site (47.6% vs. 52.2%; p<0.05) and had higher rates of micro- and macroscopic residual tumor following surgical resection.

CONCLUSIONS

An age over 40 is associated with decreased survival for patients with EWS. Due to the rarity of EWS in this cohort, the optimal role of systemic treatment remains unknown and has yet to be clearly elucidated. Consequently, our findings suggest that older patients receive disparities in treatment which may be contributing to decreased survival rates.

BACKGROUND

Ewing sarcoma (EWS) is a malignancy which primarily arises in adolescence and has been studied extensively in this population. Much less is www.mdedge.com/fedprac/avaho SEPTEMBER 2023 • S23 known about the rare patient cohort over the age of 40 at diagnosis. In this study, we describe the survival outcomes and clinical characteristics of this population.

METHODS

This retrospective cohort study utilized the National Cancer Database (NCDB) to identify 4600 patients diagnosed between 2004 through 2019. Of these patients, 4058 were under the age of 40 and 542 were over 40. Multivariate Cox regression models and Kaplan- Meier curves were used to estimate survival from diagnosis to death between age groups. Chi-square tests were used to compare demographic and socioeconomic patient characteristics. IBM SPSS version 27.0 was used. p<0.05 was used to indicate statistical significance.

RESULTS

EWS patients older than 40 experienced worse survival outcomes compared to patients under the age of 40. 5-year survival was 43.5% for older patients vs. 64.5% for younger patients (p<0.05). A multivariate Cox proportional hazards model showed that age was independently associated with inferior survival. (HR 2.23; p<0.05). EWS patients over the age of 40 were more likely to have tumors originating from the vertebral column (16.2% vs. 9.6%; p<0.05), cranium (5.5% vs. 4.7%; p<0.05), and had a higher rate of axial tumors (43.3% vs. 32.4%; p<0.05) compared to patients under 40. Additionally, patients older than 40 experienced a significantly longer delay between the date of diagnosis and initiation of systemic treatment (29.85 days vs. 19.37 days; p<0.05). Despite presenting with larger tumors , older patients were less likely to undergo a surgical procedure of the primary site (47.6% vs. 52.2%; p<0.05) and had higher rates of micro- and macroscopic residual tumor following surgical resection.

CONCLUSIONS

An age over 40 is associated with decreased survival for patients with EWS. Due to the rarity of EWS in this cohort, the optimal role of systemic treatment remains unknown and has yet to be clearly elucidated. Consequently, our findings suggest that older patients receive disparities in treatment which may be contributing to decreased survival rates.

BACKGROUND

Ewing sarcoma (EWS) is a malignancy which primarily arises in adolescence and has been studied extensively in this population. Much less is www.mdedge.com/fedprac/avaho SEPTEMBER 2023 • S23 known about the rare patient cohort over the age of 40 at diagnosis. In this study, we describe the survival outcomes and clinical characteristics of this population.

METHODS

This retrospective cohort study utilized the National Cancer Database (NCDB) to identify 4600 patients diagnosed between 2004 through 2019. Of these patients, 4058 were under the age of 40 and 542 were over 40. Multivariate Cox regression models and Kaplan- Meier curves were used to estimate survival from diagnosis to death between age groups. Chi-square tests were used to compare demographic and socioeconomic patient characteristics. IBM SPSS version 27.0 was used. p<0.05 was used to indicate statistical significance.

RESULTS

EWS patients older than 40 experienced worse survival outcomes compared to patients under the age of 40. 5-year survival was 43.5% for older patients vs. 64.5% for younger patients (p<0.05). A multivariate Cox proportional hazards model showed that age was independently associated with inferior survival. (HR 2.23; p<0.05). EWS patients over the age of 40 were more likely to have tumors originating from the vertebral column (16.2% vs. 9.6%; p<0.05), cranium (5.5% vs. 4.7%; p<0.05), and had a higher rate of axial tumors (43.3% vs. 32.4%; p<0.05) compared to patients under 40. Additionally, patients older than 40 experienced a significantly longer delay between the date of diagnosis and initiation of systemic treatment (29.85 days vs. 19.37 days; p<0.05). Despite presenting with larger tumors , older patients were less likely to undergo a surgical procedure of the primary site (47.6% vs. 52.2%; p<0.05) and had higher rates of micro- and macroscopic residual tumor following surgical resection.

CONCLUSIONS

An age over 40 is associated with decreased survival for patients with EWS. Due to the rarity of EWS in this cohort, the optimal role of systemic treatment remains unknown and has yet to be clearly elucidated. Consequently, our findings suggest that older patients receive disparities in treatment which may be contributing to decreased survival rates.