Cancer-associated non-bacterial thrombotic endocarditis-Clinical series from a single institution.

Premortem clinical presentation of cancer-associated non-bacterial thrombotic endocarditis (Ca-NBTE), therapy, and the clinal course is limited to case reports and small clinical series. An electronic search of Mayo Clinic records (03/31/2002-06/30/2022) with a subsequent manual review was performed to identify adult patients with echocardiographically detected NBTE and active malignancy, excluding those with infectious endocarditis or lupus anticoagulant/antiphospholipid antibodies. In this retrospective cohort study, we analyzed 115 Ca-NBTE patients (mean age 63.2 ± 9.7 years, 66.1% female) involving 71 (61.7%) mitral, 58 (50.4%) aortic, 8 (6.9%) tricuspid, and 1 (0.9%) pulmonary valve. The most common cancer was lung (n = 45 cases (39.1%), followed by pancreatic (n = 19, 16.5%), gynecological (17, 14.8%), gastrointestinal (n = 10, 8.7%), and 10 (8.7%) with hematologic malignancy; 6 patients had two active cancers. Embolic complications at presentation were frequent: 94 (81.7%) brain, 11 splenic, 10 renal, 6 coronary, and 4 to the extremities. Of 104 anticoagulated patients, 60 received low molecular weight heparin, 17 unfractionated heparin, 16 apixaban, 8 warfarin, and 3 rivaroxaban. There were 18 arterial thromboembolisms; the Kaplan-Meier estimates of the incidence at 2 years were consistent with a rate of 15.9% [95% Confidence Interval (CI) 9.9-23.3], including 14 strokes (12.4%, 95%CI, 7.1-19.2), and 8 other arterial emboli (10.5%, 95%CI, 4.7-18.9); there were 10 venous thromboembolisms (8.9%, 95%CI, 4.5-15.0). Fourteen major bleedings occurred (12.8%, 95%CI, 7.3-19.9) and 94 patients died during follow-up (77.9%, 95%CI, 71.1-85.8). Ca-NBTE predominantly affected women with lung adenocarcinoma or digestive tract cancers and manifested by stroke with high mortality and frequent embolic and bleeding complications during anticoagulation therapy.

Incidental pulmonary embolism in cancer and noncancer patients: Prospective cohort study.

BACKGROUND: Clinical picture and outcome of incidental pulmonary embolism (iPE) compared to symptomatic pulmonary embolism (sPE) remain unclear. METHODS: Demographics, recurrent venous thromboembolism (VTE), mortality, major bleeding, and clinically relevant nonmajor bleeding (CRNMB) were compared between iPE and sPE patients who were followed prospectively at Mayo Thrombophilia Clinic (March 1, 2013 to August 1, 2020). RESULTS: Out of 3576 VTE patients, 1417 (39.6%) had PE: 562 (39.7%) iPE and 855 sPE. Patients with cancer were more likely to have iPE (400 iPE vs. 314 sPE) compared to those without cancer (162 iPE vs. 541 sPE). VTE recurrence rate (all per 100 person-years) was similar in all iPE and sPE patients (3.34 vs. 3.68, p = .50), with cancer (4.16 vs. 4.89, p = .370), and without cancer patients (0.89 vs. 2.80, p = .25). Higher mortality observed in all patients with iPE compared to sPE (46.45 vs. 23.47, p < .001) and with cancer (56.41 vs. 45.77, p = .03) became not significant after adjustment for age, antiplatelet therapy, metastases, and cancer location. Noncancer iPE patients had higher mortality (15.95 vs. 7.18, p = .006) even after adjustment (p = .05). The major bleeding rate was also higher in all patients iPE compared to sPE (7.10 vs. 3.68, p = .03), but not after adjustment (p = .974); higher major bleeding rate in noncancer patients (6.49 vs. 1.25, p = .007) remained significant after adjustment (.02). CRNMB rate was similar to iPE and sPE patients. CONCLUSION: iPE represents a more serious clinical condition compared to sPE as indicated by the higher mortality and major bleeding but these differences reflect underlying comorbidities rather than the seriousness of the embolic event.

Venous thromboembolism after COVID-19 vaccination in patients with thrombophilia.

Patients with thrombophilia remain concerned about venous thromboembolism (VTE) risk with COVID-19 vaccinations. The aim of this study was to examine VTE outcomes in patients with inherited or acquired thrombophilia who were vaccinated for COVID-19. Vaccinated patients ≥18 years between November 1, 2020 and November 1, 2021 were analyzed using electronic medical records across the Mayo Clinic enterprise. The primary outcome was imaging confirmed acute VTE occurring 90 days before and after the date of the first vaccine dose. Thrombophilia patients were identified through laboratory testing results and ICD-10 codes. A total of 792 010 patients with at least one COVID-19 vaccination were identified. Six thousand sixty-seven of these patients were found to have a thrombophilia, among whom there was a total of 39 VTE events after compared to 51 VTE events before vaccination (0.64% vs. 0.84%, p = .20). In patients with Factor V Leiden or prothrombin gene mutation, VTE occurred in 27 patients before and in 29 patients after vaccination (0.61 vs. 0.65%, p = .79). In patients with antiphospholipid syndrome, VTE occurred in six patients before and four patients after vaccination (0.59% vs. 0.39%, p = .40). No difference was observed in the overall VTE rate when comparing the postvaccination 90 days to the prevaccination 90 days, adjusted hazard ratio 0.81 (95% confidence interval: 0.53-1.23). In this subgroup of COVID-19 vaccinated patients with thrombophilia, there was no increased risk for acute VTE postvaccination compared to the prevaccination timeframe. These results are consistent with prior studies and should offer additional reassurance to patients with inherited or acquired thrombophilia.

Bed bugs are associated with anemia.

INTRODUCTION: Bed bugs are hematophagous insects that can be problematic in some urban emergency departments. The objective was to determine if red blood cell (RBC) and coagulation indices of bed bug-infested emergency department (ED) patients differed from those of noninfested control patients. METHODS: A chart review from a single health system was performed for ED patients between February 1, 2011, and February 1, 2017. Bed bug-infested patients were matched to noninfested control patients on the basis of age, sex, and the presenting ED. Variables were analyzed with the t-test and Pearson χ2 test and were modeled with multivariable logistic regression. RESULTS: The study had 332 bed bug-infested patients and 4952 controls. Infested patients had lower hemoglobin (11.7 g/dL vs 12.8 g/dL), hematocrit (35.0% vs 37.9%), RBC counts (4.1 × 109/L vs 4.4 × 109/L), mean corpuscular volume (86.0 vs 87.5 fL/cell), and mean corpuscular hemoglobin concentrations (33.2 vs 33.7 g/dL) and higher RBC distribution width-coefficient of variation (RDW-CV) (15.2% vs 14.2%) than noninfested patients (all P ≤ .003). Infested patients were more likely to be anemic (59.5% vs 36.9%) and to have severe anemia (4.4% vs 0.7%) (P < .001 for both). Blood transfusions were more common in those with bed bugs (5.1%) than those without bed bugs (2.3%) (P < .001). CONCLUSION: Bed bug infestated patients in the ED are associated with anemia.

Impact of Thrombocytopenia on Survival in Patients with Hepatocellular Carcinoma: Updated Meta-Analysis and Systematic Review.

BACKGROUND: Platelets (PLT) have a role in the pathogenesis, progression, and prognosis of hepatocellular carcinoma (HCC) and could represent a readily measurable laboratory parameter to enhance the comprehensive evaluation of HCC patients. METHODS: The PubMed, Web of Science, and Scopus databases were searched with a focus on survival as well as patient and tumor-specific characteristics in correlation to reported PLT counts. Survival outcomes were analyzed with both common-effect and random-effects models. The hazard ratio (HR) and its 95% confidence interval (CI) from analyzed trials were incorporated. Studies that did not provide survival data but focused on platelet count correlation with HCC characteristics were reviewed. RESULTS: In total, 26 studies, including a total of 9403 patients, met our criteria. The results showed that thrombocytopenia in HCC patients was associated with poor overall survival (common-effect HR = 1.15, 95% CI: 1.06-1.25; random-effect HR = 1.30, 95% CI: 1.05-1.63). Moreover, three studies reveal significant correlations between PLT indices and tumor characteristics such as size, foci number, and etiology of HCC development. CONCLUSION: Our meta-analysis confirmed that PLT count could act as a prognostic marker in HCC, especially with a PLT count cut off <100 × 103/mm3. Further prospective studies focusing on the role of PLT in clearly defined subgroups are necessary.

Echocardiographic findings in cancer-associated non-bacterial thrombotic endocarditis. Clinical series of 111 patients from single institution.

AIMS: Echocardiographic assessment of cancer-associated non-bacterial thrombotic endocarditis (Ca-NBTE) is limited to cases reports and small clinical series. Identifying heart valves abnormalities and its relation to embolic complications and cancer types. METHODS AND RESULTS: Manual review of echocardiographic images and medical records of Mayo Clinic patients (03/31/2002-06/30/2022) was performed. Ca-NBTE in 111 patients (mean age 63.2±9.7 years, 66.7% female) predominantly affected mitral valves (MV) (69), 56 aortic (AV), 8 tricuspid (TV) and rarely pulmonic (PV) (1). In 18 patients 2 valves were involved, 3 and 4 valves involvement in only a single patient each. Embolic complications were prevalent (n=102, 91.9%). Ca-NBTE affected MV more frequently the on upstream (atrial) (90% vs 49.3%) and TV downstream (ventricular) side (75% vs 37.5%). NBTE size (cm) varied significantly among valves, with TV hosting the largest masses (0.63-2.40 x 0.39-1.77), compared to MV [(0.11-1.81 x 0.11-1.62), (length p=0.001; width p=0.03)], and to AV [(0.20-2.70 x 0.11-1.51), (length p=0.001; width p=0.056)]; MV masses were borderline longer in systemic compared to cerebral emboli (p=0.057). Majority of MV (79.6%) and AV (69.6%) had thickened leaflets. NBTE lesions commonly affected closing margins (73.9%MV, 85.7% AV, and 62.5% of TV), but rarely commissures of MV (8.7%), yet fairly frequently of AV (41.1%). Five patients had severe regurgitation of MV and 5 AV. CONCLUSION: Ca-NBTE manifests mainly as thrombotic mobile masses attached to thickened MV and AV, with distinct variations in size based on valve type. Embolic destination but not cancer type is associated with NBTE mass size, and location.

Acquired Factor VII Deficiency Associated With Chronic Myeloid Leukemia Blast Crisis.

Factor VII (FVII) is an important, vitamin K-dependent clotting factor. Acquired FVII deficiency is a rare entity that is associated with serious bleeding complications. We report a case of acquired FVII deficiency in a patient with recurrent chronic myeloid leukemia in blast crisis who developed bilateral retinal hemorrhages. The coagulopathy was corrected with the initiation of chemotherapy and subsequent reduction in peripheral blast count.

Universal Genetic Testing vs. Guideline-Directed Testing for Hereditary Cancer Syndromes Among Traditionally Underrepresented Patients in a Community Oncology Program.

Background Detection of pathogenic germline variants (PGVs) has implications for cancer screening, prognosis, treatment selection, clinical trial enrollment, and family testing. Published guidelines provide indications for PGV testing, determined by clinical and demographic factors, but their applicability in an ethnically and racially diverse community hospital population is unknown. This study describes the diagnostic and incremental yield of universal multi-gene panel testing in a diverse population in a community cancer practice. Methods We completed a prospective study of proactive germline genetic sequencing among patients with solid tumor malignancies at a community-based oncology practice in downtown Jacksonville, FL, between June 2020 and September 2021. The patients were unselected for cancer type, stage, family history, race/ethnicity, and age. PGVs identified using an 84-gene next-generation sequencing (NGS) tumor genomic testing platform were stratified by penetrance. National Comprehensive Cancer Networks (NCCN) guidelines determined incremental PGV rates. Results Two hundred twenty-three patients were enrolled, with a median age of 63 years, 78.5% female. 32.7% were Black/African American, and 5.4% were Hispanic. 39.9% of patients were commercially insured, Medicare/Medicaid insured 52.5%, and 2.7% were uninsured. The most common cancers in this cohort were breast (61.9%), lung (10.3%), and colorectal (7.2%). Twenty-three patients (10.3%) carried one or more PGVs, and 50.2% carried a variant of uncertain significance (VUS). Though there was no significant difference in the rate of PGVs based on race/ethnicity, African Americans were numerically more likely to have a VUS reported than whites (P=0.059). Eighteen (8.1%) patients had incremental clinically actionable findings that practice guidelines would not have detected, which was higher in non-whites. Conclusions In this racially/ethnically and socioeconomically diverse cohort, universal multi-gene panel testing (MGPT) increased diagnostic yield over targeted guideline-informed testing. Rates of VUS and incremental PGV were higher in non-white populations.

Risk of venous thromboembolism after COVID-19 vaccination.

BACKGROUND: COVID-19 vaccinations in the United States are effective in preventing illness and hospitalization yet concern over post-vaccination venous thromboembolism (VTE) risk has led to vaccine hesitancy. METHODS: The aim of this study was to compare VTE rates before and after COVID-19 vaccination. COVID-19 vaccinated patients ≥18 years between November 1, 2020 through November 1, 2021 were analyzed using electronic medical records across the Mayo Clinic enterprise. The primary outcome was imaging confirmed acute VTE (upper or lower deep vein thrombosis or pulmonary embolism) occurring 90 days before and after the date of first vaccine dose. RESULTS: A total of 792 010 patients with at least one COVID-19 vaccination were identified (Pfizer, n = 452 950, Moderna, n = 290 607, and Janssen [Johnson & Johnson], n = 48 453). A total of 1565 VTE events occurred in the 90 days before (n = 772) and after (n = 793) COVID-19 vaccination. VTE post-vaccination occurred in 326 patients receiving Moderna (0.11%, incidence rate [IR] 4.58 per 1000p-years), 425 patients receiving Pfizer (0.09%, IR 3.84 per 1000p-years), and 42 receiving Janssen (0.09%, IR 3.56 per 1000p-years). Compared to the pre-vaccination timeframe, the adjusted hazard ratio (aHR) for VTE after the Janssen vaccination was 0.97 (95% confidence interval [CI] 0.63-1.50), aHR 1.02 (95% CI 0.87-1.19) for Moderna, and aHR 1.00 (95% CI 0.87-1.15) for Pfizer. CONCLUSION: In this large cohort of COVID-19 vaccinated patients, no increased risk for acute VTE post-vaccination was identified for the authorized vaccines in the United States.

Investigating the association of bed bugs with infectious diseases: A retrospective case-control study.

Bed bugs are common urban pests. Unlike many other blood-feeding human ectoparasites, bed bugs are not known to be vectors of human infectious diseases, but clinical and epidemiological studies to directly interrogate this link have been limited. Here, we aimed to determine whether bed bugs were associated with infectious diseases in a set of infested patients presenting to emergency departments (ED) in the greater Cleveland, OH area. We performed a retrospective case-control study involving 332 ED patients with bed bugs and 4,952 control patients, seen from February 1, 2011, through February 1, 2017. Cases and controls were matched by age, sex, and the presenting ED. Additionally, data were adjusted for ≥20 sociodemographic variables, triage data, and comorbidities in multivariable regression analyses. Seventeen laboratory values, ten different ED and inpatient diagnoses, chest radiographs, infectious disease consults, and blood cultures were examined. The odds of bed bug infestation were significantly higher for patients that had positive blood cultures, had blood cultures growing coagulase-negative Staphylococcus, were diagnosed with pneumonia, were diagnosed with cellulitis, received an infectious disease consult, received a chest radiograph, and had higher percentages of eosinophils in the blood (P < .05 for all). Additional investigations are needed to determine whether bed bugs directly contribute to disease by transmitting causative agents, whether bed bug exposure contributes secondarily contributes to infections, or whether these associations are better explained by other environmental and social determinants of health.

Macrovascular Thrombotic Events in a Mayo Clinic Enterprise-Wide Sample of Hospitalized COVID-19-Positive Compared With COVID-19-Negative Patients.

OBJECTIVE: To determine the difference in the rate of thromboembolic complications between hospitalized coronavirus disease 2019 (COVID-19)-positive compared with COVID-19-negative patients. PATIENTS AND METHODS: Adult patients hospitalized from January 1, 2020, through May 8, 2020, who had COVID-19 testing by polymerase chain reaction assay were identified through electronic health records across multiple hospitals in the Mayo Clinic enterprise. Thrombotic outcomes (venous and arterial) were identified from the hospital problem list. RESULTS: We identified 3790 hospitalized patients with COVID-19 testing across 19 hospitals, 102 of whom had positive test results. The median age was lower in the COVID-positive patients (62 vs 67 years; P=.03). The median duration of hospitalization was longer in COVID-positive patients (8.5 vs 4 days; P<.001) and more required intensive care unit care (56.9% [58 of 102] vs 26.8% [987 of 3688]; P<.001). Comorbidities, including atrial fibrillation/flutter, heart failure, chronic kidney disease, and malignancy, were observed less frequently with COVID-positive admissions. Any venous thromboembolism was identified in 2.9% of COVID-positive patients (3 of 102) and 4.6% of COVID-negative patients (168 of 3688). The frequency of venous and arterial events was not different between the groups. The unadjusted odds ratio (OR) for COVID-positive-patients for any venous thromboembolism was 0.63 (95% CI, 0.19 to 2.02). A multivariable logistic regression model evaluated death within 30 days of hospital discharge; neither COVID positivity (adjusted OR, 1.12; 95% CI, 0.54 to 2.34) nor thromboembolism (adjusted OR, 0.90; 95% CI, 0.60 to 1.32) was associated with death. CONCLUSION: Early experience in patients with COVID-19 across multiple academic and regional hospitals representing different US regions demonstrates a lower than previously reported incidence of thrombotic events. This incidence was not higher than a contemporary COVID-negative hospitalized comparator.

Timing of venous thromboembolism diagnosis in hospitalized and non-hospitalized patients with COVID-19.

BACKGROUND: The reported incidence of venous thromboembolism (VTE) in COVID-19 patients varies widely depending on patient populations sampled and has been predominately studied in hospitalized patients. The goal of this study was to assess the evolving burden of COVID-19 and the timing of associated VTE events in a systems-wide cohort. METHODS: COVID-19 PCR positive hospitalized and non-hospitalized patients ≥18 years of age tested between 1/1/2020 through 12/31/2020 were retrospectively analyzed using electronic medical records from multiple states across the Mayo Clinic enterprise. Radiology reports within 90 days before and after confirmed COVID-19 diagnosis were examined for VTE outcomes using validated Natural Language Processing (NLP) algorithms. RESULTS: A 29-fold increased rate of VTE compared to the pre-COVID-19 period was noted during the first week following the first positive COVID-19 test (RR: 29.39; 95% CI 21.77-40.03). The rate of VTE steadily decreased and returned to baseline by the 6th week. Among 366 VTE events, most occurred during (n = 243, 66.3%) or after (n = 111, 30.3%) initial hospitalization. Only 11 VTE events were identified in patients who did not require hospitalization (3.0% of total VTE events). VTE and mortality increased with advancing age with a pronounced increased each decade in older patients. CONCLUSION: We observed a profoundly increased risk of VTE within the first week after positive testing for COVID-19 that returned to baseline levels after 6 weeks. VTE events occurred almost exclusively in patients who were hospitalized, with the majority of VTE events identified within the first days of hospitalization.

Identification and Management of Abdominal Wall Varices in Pregnancy.

BACKGROUND: Portal hypertension in pregnancy is associated with elevated risk of variceal hemorrhage. Ectopic varices, those located outside the esophagus or stomach, are rare but have a high risk of associated maternal morbidity or mortality. CASE: A 31-year-old woman, gravida 2 para 0010, with cirrhosis and portal hypertension was found to have abdominal wall ectopic varices on third-trimester obstetric ultrasonography. Computed tomography angiography confirmed these findings. Given concern for catastrophic hemorrhage during delivery, she underwent transjugular intrahepatic portosystemic shunt placement at 35 weeks of gestation, with reduction in the pressure gradient within the portosystemic circulation. She subsequently underwent an uncomplicated cesarean delivery. CONCLUSION: Identification of ectopic varices on obstetric ultrasonography may allow for treatment before delivery, decreasing the risk of serious maternal morbidity or mortality.

Ovarian Vein Thrombosis: Incidence of Recurrent Venous Thromboembolism and Survival.

OBJECTIVE: To identify the risk of venous thromboembolism recurrence, major bleeding, and mortality in patients with ovarian vein thrombosis so as to better define optimal treatment strategies. METHODS: Patients with ovarian vein thrombosis (1990-2015) and age- and gender-matched patients with contemporary leg deep vein thrombosis (DVT) were assessed for differences in etiology, venous thromboembolism recurrence, and survival in a case-control study. RESULTS: Over the timeframe of this study, only 219 ovarian vein thrombosis cases were identified compared with 13,417 leg DVTs. Median duration of follow-up was 1.23 years (interquartile range 0.25-4.14). Pulmonary embolism was identified at presentation in 6% of patients with ovarian vein thrombosis and 16% of those with DVT (P=.001). Frequent causes of ovarian vein thrombosis included cancer, hormonal stimulation, surgery, and hospitalization. Cancer was twofold more frequent in patients with ovarian vein thrombosis (44% compared with 21%; P<.01). Despite being less frequently treated with anticoagulation (ovarian vein thrombosis 54% compared with DVT 98%, P<.001), venous thromboembolism recurrence rates were similar between groups (ovarian vein thrombosis 2.3 compared with DVT 1.8 per 100 patient-years, P=.49). A personal history of venous thromboembolism and preceding surgery was found to be an independent risk factor for venous thromboembolism recurrence among those treated with anticoagulation (hazard ratio 6.7, P=.04 and hazard ratio 13.6, P=.03, respectively). There was no significant difference in overall survival. CONCLUSION: Ovarian vein thrombosis is a rare thrombotic condition with an incidence 60-fold lower compared with leg DVT in our institution. The striking association with cancer adversely affects overall survival rates in patients with ovarian vein thrombosis. Venous thromboembolism recurrence rates argue for anticoagulation with a direct oral anticoagulant or vitamin K antagonist, particularly in those with a history of venous thromboembolism.

Ovarian vein thrombosis: incidence of recurrent venous thromboembolism and survival.

For patients with ovarian vein thrombosis (OVT), neither the rate of recurrence nor the expected survival are well established. Clarification of these natural history data would aid in defining the optimal management. We studied all female patients with OVT seen at the Mayo Clinic between 1990 and 2006. Survival, recurrent venous thrombosis rates, and prothrombotic factors were compared to a randomly selected group of 114 female patients with lower extremity venous thrombosis (DVT). Patients with OVT (n = 35; mean age 44.8 +/- 17.9 years) were significantly more likely to be under hormonal stimulation (48%), have an underlying malignancy (34%), experienced recent pelvic infection (23%) or undergone recent surgery (20%), compared to DVT patients. During a mean follow-up period of 34.6 +/- 44.3 months, three patients suffered three recurrent venous thrombi (event rate: three per 100 patient years of follow-up). This recurrence rate was comparable to patients with lower extremity DVT (2.2 per 100 patient years). Recurrent thrombosis involved the contralateral ovarian vein, left renal vein, and inferior vena cava. The five-year mortality rate for OVT patients was 43% compared to 20% for DVT patients (p = 0.08). All OVT deaths were cancer related. Survival was greater in OVT patients without cancer compared to those with active cancer (p < 0.0001). In conclusion, venous thromboembolism recurrence rates are low and comparable to lower extremity DVT. Therefore general treatment guidelines for lower extremity DVT may be applicable. Poor survival rates in OVT are principally governed by the presence of malignancy.

A Case of Hypophosphatemia with Increased Urinary Excretion of Phosphorus Associated with Ibrutinib.

Ibrutinib, an irreversible oral inhibitor of Bruton's tyrosine kinase, has been used in the treatment of patients with multiple hematologic malignancies. A 59-year-old male with chronic lymphocytic leukemia was treated with 420 mg/day of ibrutinib. No evidence of bruising or diarrhea was noted. The treatment was complicated by a transient increase in creatinine (from a baseline of 1.2 to 1.5 mg/dl) and potassium (reaching a peak of 6.5 mEq/l). Uric acid and calcium levels were normal. The patient developed hypophosphatemia (prior to initiation of therapy the serum phosphorus was 2.9 mg/dl). No metabolic acidosis was noted. Urinalysis showed no glucosuria or proteinuria. Urinary fraction of excretion of phosphate was found to be 345% (normal <5%). Because of these changes, ibrutinib was held, and the patient was given kayexalate. Serum potassium normalized. Serum phosphorus was checked a couple of weeks later and also normalized. A lower dose of ibrutinib (140 mg/day) was restarted. Upon follow-up, the phosphorus level has been between 2.9 and 3.2 mg/dl. No further evidence of hyperkalemia has been noted. Renal function has remained at baseline. To the best of our knowledge, this is the first case report describing the mechanism of hypophosphatemia in a patient treated with ibrutinib.

von Willebrand Factor Abnormalities and Heyde Syndrome in Dysfunctional Heart Valve Prostheses.

IMPORTANCE: Limited data suggest that von Willebrand factor (VWF) abnormalities may accompany the high-shear state associated with prosthetic valve dysfunction. If true, laboratory testing could add value in quantifying prosthesis dysfunction and could suggest a pathophysiological explanation for acquired bleeding in some patients. OBJECTIVES: To determine whether dysfunctional valve prostheses are associated with VWF abnormalities compared with normally functioning valve prostheses, to identify the severity of the VWF abnormality relative to other conditions, and to describe associated bleeding and the occurrence of gastrointestinal angiodysplasia. DESIGN, SETTING, AND PARTICIPANTS: Cohort study in a multispecialty practice setting from August 2010 through November 2015. To assess the severity of VWF dysfunction, data were compared with those from previously reported healthy controls and patients with aortic stenosis, mitral regurgitation, and left ventricular assist devices. Patients underwent assessment of multiple VWF laboratory tests and echocardiography. MAIN OUTCOMES AND MEASURES: Loss of high-molecular-weight multimers of VWF. RESULTS: A total of 136 patients were included in this study. During the study period, we assessed 26 patients with normally functioning surgical or transcatheter aortic valve replacement, 24 patients with dysfunctional aortic valve replacement, 36 patients with normally functioning mitral valve replacement or repair, 19 patients with dysfunctional mitral valve replacement or repair, and 31 patients with native aortic regurgitation without coexisting aortic stenosis. von Willebrand factor multimers were abnormal in 1 of 26 normal aortic valve replacements and in 2 of 36 normal mitral valve replacements or repairs but were abnormal in 20 of 24 dysfunctional aortic valve replacements and in 14 of 19 dysfunctional mitral valve replacements or repairs (P < .001 for both). Normal aortic valve replacement also had a higher VWF activity to antigen ratio, mean (range) 0.94 (0.84-0.99) compared to dysfunctional aortic valve replacement, 0.78 (0.73-0.87), P < .001, as did normal mitral valve replacement or repair, 0.90 (0.86-0.93) compared to dysfunctional mitral valve replacement or repair, 0.78 (0.70-0.90), P = .005. Platelet function analyzer closure times were lower with normal aortic valve replacement, mean (range) 92 (82-112) seconds compared to dysfunctional aortic valve replacement, 139 (122-177) seconds, P < .001, and also in normally functioning mitral valve replacement or repair, 85 (74-96) seconds compared to dysfunctional mitral valve replacement or repair, 143 (128-192) seconds, P < .001. Gastrointestinal bleeding was noted in 6 of 24 patients with aortic prosthesis dysfunction and in 5 of 19 patients with mitral prosthesis/repair dysfunction and was associated with a lower normalized VWF multimer ratio than in patients without bleeding. Gastrointestinal angiodysplasia was noted in 5 of 6 bleeding patients with dysfunctional aortic prostheses and in 3 of 5 bleeding patients with dysfunctional mitral prostheses/repair. CONCLUSIONS AND RELEVANCE: Acquired abnormalities of VWF multimers are associated with aortic and mitral prosthesis dysfunction, with occasional gastrointestinal bleeding and gastrointestinal angiodysplasia. Quantitative VWF tests may provide adjunctive value in the difficult assessment of prosthetic valve dysfunction.

Periprocedural Anticoagulation Management of Patients with Thrombophilia.

BACKGROUND: Appropriate periprocedural management of the chronically anticoagulated patient with an inherited or acquired thrombophilia is uncertain. The objective of this study was to test "thrombophilia" as a potential predictor of the 3-month cumulative incidence of thromboembolism and major bleeding among chronically anticoagulated patients undergoing an invasive procedure. METHODS: In a prospective cohort study, consecutive chronically anticoagulated patients referred to the Mayo Thrombophilia Center for standardized periprocedural anticoagulation management who had venous thromboembolism and complete thrombophilia testing were categorized as "severe," "non-severe," or "no identifiable" thrombophilia. The 3-month cumulative incidence rates of thromboembolism, bleeding, and death were estimated using the Kaplan-Meier product limit method. RESULTS: Among 362 patients with complete thrombophilia testing, 165 (46%) had a defined thrombophilia; 76 patients had severe thrombophilia, mainly due to antiphospholipid syndrome (66%). Half of the patients in each of the 3 groups received pre- and postprocedure heparin. During follow-up, there were no thromboembolic events, rare major bleeding events (1% for each group), and 4 deaths. Due to the very low event rates for each of these outcomes, Cox proportional hazard modeling could not be performed. CONCLUSIONS: Periprocedural event rates were low irrespective of thrombophilia status. Inherited or acquired thrombophilia was not a predictor of thromboembolism, major bleeding, or mortality after temporary interruption of chronic anticoagulation for an invasive procedure.

Usefulness of Von Willebrand Factor Activity Indexes to Predict Therapeutic Response in Hypertrophic Cardiomyopathy.

Degraded by shear stress, loss of high-molecular-weight multimers of von Willebrand factor (VWF) correlates strongly with pressure gradient in aortic stenosis (AS) and obstructive hypertrophic cardiomyopathy (HC). We assessed VWF tests before and after interventions in HC and contrasted the severity of abnormalities in HC to patients with AS, mitral regurgitation, and left ventricular assist devices. Ninety patients with median (interquartile range) age 66 (53 to 72) years, 51% men, with HC had assessments of 3 VWF parameters and B-type natriuretic peptide before and after 26 discreet medical/pacing interventions, 22 alcohol septal ablations, and 28 ventricular septal myectomies. VWF multimers were abnormal in 87% of patients with obstructive HC versus 48% of patients with latent obstruction (p = 0.0001). VWF measurements correlated with peak instantaneous left ventricular outflow tract gradient, Spearman ρ 0.51 to 0.61, p <0.0001. For B-type natriuretic peptide, correlation with left ventricular outflow tract gradient was weaker, ρ = 0.37, p = 0.0005, but stronger with septal thickness or mitral E/e'. In pre-/post-medical treatment of HC, VWF multimers were abnormal in 73%/68% of patients, p = 0.74; pre-/post-septal ablation 74%/26%, p = 0.0035; and pre-/post-septal myectomy 75%/0%, p <0.0001. In obstructive HC, the degree VWF multimer loss was greater than in severe AS or severe mitral regurgitation and overlapped that seen in left ventricular assist devices. In conclusion, VWF activity indexes were predictably abnormal in patients with HC with resting obstruction to a degree where bleeding could be anticipated, accurately reflected gradient changes after intervention, and demonstrated complete normalization after septal myectomy.