Combined immunosuppression for acquired hemophilia A: CyDRi is a highly effective low-toxicity regimen.

Acquired hemophilia A (AHA) is a rare severe autoimmune bleeding disorder with significant morbidity and mortality. Although critical for disease control, there is no consensus for the best immunosuppressive regimen. Most authors use steroids first line, followed by other agents for steroid failures. Upfront combined regimens offer the advantage of reduced steroid exposure and toxicity as well as increased efficacy. We retrospectively analyzed data from 32 patients with AHA treated on an identical such institutional protocol: cyclophosphamide 1000 mg on days 1 and 22, dexamethasone 40 mg on days 1, 8, 15, and 22, and rituximab 100 mg on days 1, 8, 15, and 22 (the regimen was termed CyDRi). All patients received at least 1 cycle of CyDRi. If necessary, CyDRi was repeated until remission, no sooner than day 43 of the previous cycle. Bleeding control was rapidly achieved. The median time for bleeding control was 15.5 days (range, 0-429 days; interquartile range, 2.5-29.5 days). Thirty-one (96.8%) of 32 patients achieved durable complete remission (CR); 29 (90.6%) of 32 patients were alive at last follow-up, all of them in CR. The median time to reach first CR was 77 days (range, 19-939 days; interquartile range, 31-115 days). Toxicity and side effects were acceptable and milder than those of commonly used, prolonged steroid therapies. In conclusion, the CyDRi regimen produced markedly higher CR rates and overall survival than currently used sequential regimens. Taken together, CyDRi proved to be an attractive option for the immunosuppression of elderly patients with AHA.

Tetrameric Acetyl-CoA Acetyltransferase 1 Is Important for Tumor Growth.

Mitochondrial acetyl-CoA acetyltransferase 1 (ACAT1) regulates pyruvate dehydrogenase complex (PDC) by acetylating pyruvate dehydrogenase (PDH) and PDH phosphatase. How ACAT1 is "hijacked" to contribute to the Warburg effect in human cancer remains unclear. We found that active, tetrameric ACAT1 is commonly upregulated in cells stimulated by EGF and in diverse human cancer cells, where ACAT1 tetramers, but not monomers, are phosphorylated and stabilized by enhanced Y407 phosphorylation. Moreover, we identified arecoline hydrobromide (AH) as a covalent ACAT1 inhibitor that binds to and disrupts only ACAT1 tetramers. The resultant AH-bound ACAT1 monomers cannot reform tetramers. Inhibition of tetrameric ACAT1 by abolishing Y407 phosphorylation or AH treatment results in decreased ACAT1 activity, leading to increased PDC flux and oxidative phosphorylation with attenuated cancer cell proliferation and tumor growth. These findings provide a mechanistic understanding of how oncogenic events signal through distinct acetyltransferases to regulate cancer metabolism and suggest ACAT1 as an anti-cancer target.

Tyr phosphorylation of PDP1 toggles recruitment between ACAT1 and SIRT3 to regulate the pyruvate dehydrogenase complex.

Mitochondrial pyruvate dehydrogenase complex (PDC) is crucial for glucose homeostasis in mammalian cells. The current understanding of PDC regulation involves inhibitory serine phosphorylation of pyruvate dehydrogenase (PDH) by PDH kinase (PDK), whereas dephosphorylation of PDH by PDH phosphatase (PDP) activates PDC. Here, we report that lysine acetylation of PDHA1 and PDP1 is common in epidermal growth factor (EGF)-stimulated cells and diverse human cancer cells. K321 acetylation inhibits PDHA1 by recruiting PDK1, and K202 acetylation inhibits PDP1 by dissociating its substrate PDHA1, both of which are important in promoting glycolysis in cancer cells and consequent tumor growth. Moreover, we identified mitochondrial ACAT1 and SIRT3 as the upstream acetyltransferase and deacetylase, respectively, of PDHA1 and PDP1, while knockdown of ACAT1 attenuates tumor growth. Furthermore, Y381 phosphorylation of PDP1 dissociates SIRT3 and recruits ACAT1 to PDC. Together, hierarchical, distinct posttranslational modifications act in concert to control molecular composition of PDC and contribute to the Warburg effect.

Therapeutic plasma exchange for COVID-19-associated hyperviscosity.

BACKGROUND: Recent data suggests an association between blood hyperviscosity and both propensity for thrombosis and disease severity in patients with COVID-19. This raises the possibility that increased viscosity may contribute to endothelial damage and multiorgan failure in COVID-19, and that therapeutic plasma exchange (TPE) to decrease viscosity may improve patient outcomes. Here we sought to share our experience using TPE in the first 6 patients treated for COVID-19-associated hyperviscosity. STUDY DESIGN AND METHODS: Six critically ill COVID-19 patients with plasma viscosity levels ranging from 2.6 to 4.2 centipoise (cP; normal range, 1.4-1.8 cP) underwent daily TPE for 2-3 treatments. RESULTS: TPE decreased plasma viscosity in all six patients (Pre-TPE median 3.75 cP, range 2.6-4.2 cP; Post-TPE median 1.6 cP, range 1.5-1.9 cP). TPE also decreased fibrinogen levels in all five patients for whom results were available (Pre-TPE median 739 mg/dL, range 601-1188 mg/dL; Post-TPE median 359 mg/dL, range 235-461 mg/dL); D-dimer levels in all six patients (Pre-TPE median 5921 ng/mL, range 1134-60 000 ng/mL; Post-TPE median 4893 ng/mL, range 620-7518 ng/mL); and CRP levels in five of six patients (Pre-TPE median 292 mg/L, range 136-329 mg/L; Post-TPE median 84 mg/L, range 31-211 mg/L). While the two sickest patients died, significant improvement in clinical status was observed in four of six patients shortly after TPE. CONCLUSIONS: This series demonstrates the utility of TPE to rapidly correct increased blood viscosity in patients with COVID-19-associated hyperviscosity. Large randomized trials are needed to determine whether TPE may improve clinical outcomes for patients with COVID-19.

Venous Thromboembolism: Genetics and Thrombophilias.

Venous thromboembolism (VTE) is a major cause of morbidity and mortality throughout the world. Up to one half of patients who present with VTE will have an underlying thrombophilic defect. This knowledge has led to a widespread practice of testing for such defects in patients who develop VTE. However, identifying a hereditary thrombophilia by itself does not necessarily change outcomes or dictate therapy. Furthermore, family history of VTE by itself can increase an asymptomatic person's VTE risk several-fold, independent of detecting a known inherited thrombophilia. In this article, we will describe the current validated hereditary thrombophilias including their history, prevalence, and association with VTE. With a focus on evaluating both risks and benefits of testing, we will also explore the controversies of why, who, and when to test as well as discuss contemporary societal guidelines. Lastly, we will share how these tests have been integrated into clinical practice and how to best utilize them in the future.

Predicting early blast transformation in chronic-phase chronic myeloid leukemia: is immunophenotyping the missing link?

BACKGROUND: Flow cytometry (FC) is a commonly requested test in the workup of leukocytosis in community practices. The role of FC in chronic-phase chronic myeloid leukemia (CP-CML) is unknown. We hypothesized that finding aberrant cells with FC in CP-CML may predict early blast-phase (BP) transformation. METHODS: Results for FC performed at the time of diagnosis for adult and pediatric patients with CP-CML who were referred to our institution were reviewed, and they were correlated with outcomes. RESULTS: FC was performed at the time of diagnosis for 110 of 233 patients (47%) with CP-CML. Aberrant populations, representing a median of 2% (range, 0.3%-15%), were detected with FC in 30% of patients (33 of 110): 2 of these 33 patients expressed lymphoid markers, and 31 expressed aberrant myeloid markers. Patients received imatinib (85%), dasatinib (12%), or nilotinib (3%) as their first-line treatment. With a median follow-up of 43 months (range, 2-113 months), chronic myeloid leukemia transformed to BP in 5 of the 33 patients. The 2 patients with lymphoid markers and the 3 of 31 patients with aberrant myeloid markers experienced a transformation to lymphoid BP at a median of 11 months (range, 4-72 months) after the initiation of tyrosine kinase inhibitor therapy. Although both cases with detectable lymphoid markers rapidly progressed to lymphoid BP, the positive predictive value of BP transformation by the detection of myeloid aberrant cells with FC was only 10% (3 of 31). CONCLUSIONS: In contrast to aberrant myeloid markers, the detection of lymphoid markers by FC at the time of the diagnosis of CP-CML appears to be associated with early progression to lymphoid BP.

Symptoms and Impaired Quality of Life After COVID-19 Hospitalization: Effect of Therapeutic Heparin in Non-ICU Patients in the Accelerating COVID-19 Therapeutic Interventions and Vaccines 4 Acute Trial: Effect on 3-Month Symptoms and Quality of Life.

BACKGROUND: Therapeutic-dose heparin decreased days requiring organ support in noncritically ill patients hospitalized for COVID-19, but its impact on persistent symptoms or quality of life (QOL) is unclear. RESEARCH QUESTION: In the Accelerating COVID-19 Therapeutic Interventions and Vaccines 4 ACUTE (ACTIV-4a) trial, was randomization of patients hospitalized for COVID-19 illness to therapeutic-dose vs prophylactic heparin associated with fewer symptoms and better QOL at 90 days? STUDY DESIGN AND METHODS: This was an open-label randomized controlled trial at 34 hospitals in the United States and Spain. A total of 727 noncritically ill patients hospitalized for COVID-19 from September 2020 to June 2021 were randomized to therapeutic-dose vs prophylactic heparin. Only patients with 90-day data on symptoms and QOL were analyzed. We ascertained symptoms and QOL by the EQ-5D-5L at 90-day follow-up in a preplanned analysis for the ACTIV-4a trial. Individual domains assessed by the EQ-5D-5L included mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Univariate and multivariate analyses were performed. RESULTS: Among 571 patients, 288 (50.4%) reported at least one symptom. Among 410 patients, 148 (36.1%) reported moderate to severe impairment in one or more domains of the EQ-5D-5L. The presence of 90-day symptoms was associated with moderate-severe impairment in the EQ-5D-5L domains of mobility (adjusted OR [aOR], 2.37; 95% CI, 1.22-4.59), usual activities (aOR, 3.66; 95% CI, 1.75-7.65), pain (aOR, 2.43; 95% CI, 1.43-4.12), and anxiety (aOR, 4.32; 95% CI, 2.06-9.02), compared with patients reporting no symptoms There were no differences in symptoms or in the overall EQ-5D-5L index score between treatment groups. Therapeutic-dose heparin was associated with less moderate-severe impairment in all physical functioning domains (mobility, self-care, usual activities) but was independently significant only in the self-care domain (aOR, 0.32; 95% CI, 0.11-0.96). INTERPRETATION: In a randomized controlled trial of hospitalized noncritically ill patients with COVID-19, therapeutic-dose heparin was associated with less severe impairment in the self-care domain of EQ-5D-5L. However, this type of impairment was uncommon, affecting 23 individuals. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT04505774; URL: www. CLINICALTRIALS: gov.

Epsilon aminocaproic acid prevents bleeding in severely thrombocytopenic patients with hematological malignancies.

BACKGROUND: Despite prophylactic platelet transfusions, bleeding remains a significant problem in thrombocytopenic patients. METHODS: The antifibrinolytic agent epsilon aminocaproic acid (EACA) was administered to 44 chronically (median duration, 273 days) and severely (platelet count, 8 × 10(9)/L; range, 1 × 10(9)/L-19 × 10(9)/L) thrombocytopenic patients with hematological malignancies. Prophylactic EACA at a dose of 1 g twice daily was orally administered for a median duration of 47 days (range, 7 days-209 days) until the platelet count recovered to > 30; × 10(9) /L. Platelets were only transfused if bleeding occurred. RESULTS: While receiving EACA, 59% of the patients did not bleed, 25% had 19 episodes of spontaneously resolving minor bleeding that did not require platelet transfusion, and 16% received a median of 4 platelet transfusions (range, 1 transfusion-8 transfusions) for 1 major traumatic and 9 spontaneous grade 2 to grade 3 bleeding (based on the World Health Organization classification of idiopathic thrombocytopenic purpura). No EACA toxicities were noted, and venous thromboses were not observed. CONCLUSIONS: EACA is well tolerated and is associated with a low risk of major bleeding in patients with hematological malignancies who are experiencing chronic severe thrombocytopenia.

Comparison of Venous Thromboembolism Outcomes after COVID-19 and Influenza Vaccinations.

Background Published data on the risk of venous thromboembolism (VTE) with coronavirus disease 2019 (COVID-19) vaccines are scarce and inconclusive, leading to an unmet need for further studies. Methods A retrospective, multicentered study of adult patients vaccinated for one of the three approved COVID-19 vaccines in the United States of America and a pre-COVID-19 cohort of patients vaccinated for influenza at two institutions: Mayo Clinic Enterprise sites and the Medical College of Wisconsin, looking at rate of VTE over 90 days. VTE was identified by applying validated natural language processing algorithms to relevant imaging studies. Kaplan-Meier curves were used to evaluate rate of VTE and Cox proportional hazard models for incident VTE after vaccinations. Sensitivity analyses were performed for age, sex, outpatient versus inpatient status, and type of COVID-19 vaccine. Results A total of 911,381 study subjects received COVID-19 vaccine (mean age: 56.8 [standard deviation, SD: 18.3] years, 55.3% females) and 442,612 received influenza vaccine (mean age: 56.5 [SD: 18.3] years, 58.7% females). VTE occurred within 90 days in 1,498 (0.11%) of the total 1,353,993 vaccinations: 882 (0.10%) in the COVID-19 and 616 (0.14%) in the influenza vaccination cohort. After adjusting for confounding variables, there was no difference in VTE event rate after COVID-19 vaccination compared with influenza vaccination (adjusted hazard ratio: 0.95 [95% confidence interval: 0.85-1.05]). No significant difference in VTE rates was observed between the two cohorts on sensitivity analyses. Conclusion In this large cohort of COVID-19-vaccinated patients, risk of VTE at 90 days was low and no different than a pre-COVID-19 cohort of influenza-vaccinated patients.

Primary Care Clinicians' Prescribing Patterns of Reduced-Dose Direct Oral Anticoagulants for Extended-Phase Venous Thromboembolism Treatment.

The direct anticoagulants (DOACs), apixaban and rivaroxaban, are used for extended-phase treatment of venous thromboembolism (VTE) and have labeling for dose reduction for this indication. The objective of this study was to better understand primary care clinician prescribing patterns of apixaban and rivaroxaban for extended-phase anticoagulation. We conducted a 21-question survey targeting members of the American College of Physicians and United States Veterans Administration anticoagulation management services. Survey questions covered prescribing behaviors for dose reduction of apixaban and rivaroxaban for extended VTE treatment, as well as questions related to the respondent's practice setting. We used logistic regression to assess associations between demographics and prescribing behaviors. We used k-means clustering to identify distinct groups of prescribing patterns. Among 227 respondents, most were attending physicians (60%) and one-third (34%) practiced in internal medicine or primary care. Most (59%) indicated they dose-reduced DOACs. Hospitalists (no outpatient care) were least likely to dose-reduce (OR 0.09 [95% CI 0.03-0.22]), as well as early-career clinicians (0.53 [0.30-0.91]). Pharmacists and clinicians who treat over 500 VTE patients annually were most likely to dose reduce (6.4 [2.9-16.3]), (2.9 [1.5-6.0]), respectively. We identified five clusters of dosing behaviors and characterized clinician makeup. Clusters were primarily differentiated by frequency of dose reduction, DOAC preference, and temporary re-escalation of doses. We identified clinician characteristics that are associated with dose-reduction prescribing behaviors; these analyses provide insight into where targeted interventions, such as protocolization and education, would be most beneficial.

Comparing direct oral anticoagulants and vitamin K antagonist use in morbidly obese patients with venous thromboembolism: A single center retrospective cohort study.

Introduction: Limited data exists on the safety and efficacy of direct-acting oral anticoagulants (DOAC) use in morbidly obese patients with venous thromboembolism (VTE). Given the benefits of DOAC use over vitamin K antagonists (VKAs), in terms of monitoring requirements, and dietary and drug interactions, it is important to evaluate whether this is consistent in the higher risk for VTE recurrence morbidly obese group body mass index (BMI ≥ 40 kg/m2). Materials and methods: This retrospective, single-center cohort study included patients with a BMI of at least 40 kg/m2 who were admitted to Emory University Hospital from 1st January 2012 to 31st May 2020 with acute VTE, and subsequently initiated on anticoagulation treatment with either DOAC or VKA (warfarin). Univariate and bivariate analyses were used to evaluate differences in demographics by treatment type and BMI. Multivariate Cox proportional hazard regression was used to assess the risk of VTE recurrence by type of treatment among morbidly obese patient subgroup. Results: There were 247 (11.8%) morbidly obese (≥ 40 kg/m2) patients who were more likely than non-obese patients to be younger, female, and of non-white race. Thirty percent of the study population (n=74) had a BMI >50 kg/m2. T ime-to-event analysis confirmed that the hazard of experiencing a recurrent thrombosis was not statistically significantly different among morbidly obese patients treated with a DOAC compared with VKA (hazard ratio [HR]: 0.28, confidence interval [CI] 0.07-1.11, p = 0.07). Conclusions: This study aligns with previous literature and confirms that morbidly obese patients receiving DOAC or VKA have similar risks of recurrent VTE.

Physician perceptions and use of reduced-dose direct oral anticoagulants for extended phase venous thromboembolism treatment.

Background: The direct oral anticoagulants (DOACs), apixaban and rivaroxaban, have been studied for extended-phase treatment of venous thromboembolism (VTE). Yet, scant evidence exists surrounding clinician practice and decision-making regarding dose reduction. Aims: Report clinician practice and characteristics surrounding dose reduction of DOACs for extended-phase VTE treatment. Methods: We conducted a 16-question REDCap survey between July 14, 2021, and September 13, 2021, among ISTH 2021 Congress attendees and on Twitter. We explored factors associated with dose reduction using logistic regression. We used k-means clustering to identify distinct groups of dose-reduction decision-making. Random forest analysis explored demographics with respect to identified groups. Results: Among 171 respondents, most were attending academic physicians from North America. Clinicians who treated larger volumes of patients had higher odds of dose reduction. We identified five clusters that showed distinct patterns of behavior regarding dose reduction. Cluster 1 rarely dose reduces and likely prescribes rivaroxaban over apixaban; cluster 2 dose reduces frequently, does not consider age when dose-reducing, is least likely to temporarily reescalate dosing, and prescribes apixaban and rivaroxaban equally; cluster 3 dose reduces <50% of the time, and temporarily reescalates dosing during increased VTE risk; cluster 4 dose reduces frequently, temporarily reescalates dosing, and is most likely to prescribe apixaban over rivaroxaban; and cluster 5 dose reduces most frequently, and takes the fewest risk factors into consideration when deciding to dose reduce. Conclusions: Most clinicians elect to dose-reduce DOACs for extended-phase anticoagulation. The likelihood of a clinician to dose reduce increases with volume of patients treated. Clinician prescribing patterns cluster around VTE risk factors as well as reescalation during high-risk periods.

Clinical Outcomes of Critically III Patients with COVID-19 by Race.

BACKGROUND: Studies of COVID-19 have shown that African Americans have been affected by the virus at a higher rate compared to other races. This cohort study investigated comorbidities and clinical outcomes by race among COVID-19 patients admitted to the intensive care unit. METHODS: This is a case series of critically ill patients admitted with COVID-19 to an academic healthcare system in Atlanta, Georgia. The study included all critically ill hospitalized patients between March 6, 2020, and May 5, 2020. Clinical outcomes during hospitalization included mechanical ventilation, renal replacement therapy, and mortality stratified by race. RESULTS: Of 288 patients included (mean age, 63 ± 16 years; 45% female), 210 (73%) were African American. African Americans had significantly higher rates of comorbidities compared to other races, including hypertension (80% vs 59%, P = 0.001), diabetes (49% vs 34%, P = 0.026), and mean BMI (33 kg/m2 vs 28 kg/m2, P < 0.001). Despite African Americans requiring continuous renal replacement therapy during hospitalization at higher rates than other races (27% vs 13%, P = 0.011), rates of intubation, intensive care unit length of stay, and overall mortality (30% vs 24%, P = 0.307) were similar. CONCLUSION: This racially diverse series of critically ill COVID-19 patients shows that despite higher rates of comorbidities at hospital admission in African Americans compared with other races, there was no significant difference in mortality.

Interdisciplinary Approach to Thrombosis Management in COVID-19 at a Large Academic Center.

There is an increasing recognition of association of COVID-19 with a distinct coagulopathy and increased risk of thrombosis. Unfortunately, effective strategies to prevent and treat thrombosis in this patient population remain uncertain. In the setting of a worsening pandemic, there is an urgent need to provide practical guidance to the clinicians on management of the coagulopathy, while waiting for the results from large systematic trials to establish best practices. At our institution, we convened an interdisciplinary group of 25 experts in the field of thrombosis from different medical specialties to review available literature and brainstorm management strategies. The group provided a 3-tiered anticoagulation algorithm for patients with COVID-19 along with a pathway for multidisciplinary review of difficult or refractory cases, which are described in this manuscript. In these unprecedented times where medical decision making is made difficult by both the novelty of the disease and paucity of robust data, clinical algorithms such as the one presented here may prove to be helpful for frontline providers caring for individual patients.

COVID-19-associated venous thromboembolism portends worse survival.

Patients with coronavirus disease 2019 (COVID-19) seem to be at high risk for venous thromboembolism (VTE) development, but there is a paucity of data exploring both the natural history of COVID-19-associated VTE and the risk for poor outcomes after VTE development. This investigation aims to explore the relationship between COVID-19-associated VTE development and mortality. A prospectively maintained registry of patients older than 18 years admitted for COVID-19-related illnesses within an academic health care network between March and September 2020 was reviewed. Codes from the tenth revision of the International Classification of Diseases for VTE were collected. The charts of those patients with a code for VTE were manually reviewed to confirm VTE diagnosis. There were 2,552 patients admitted with COVID-19-related illnesses. One hundred and twenty-six patients (4.9%) developed a VTE. A disproportionate percentage of patients of Black race developed a VTE (70.9% VTE v 57.8% non-VTE; P = .012). A higher proportion of patients with VTE expired during their index hospitalization (22.8% VTE v 8.4% non-VTE; P < .001). On multivariable logistic regression analysis, VTE was independently associated with mortality (odds ratio = 3.17; 95% confidence interval, 1.9-5.2; P < .001). Hispanic/Latinx ethnicity was associated with decreased mortality (odds ratio = 0.45; 95% confidence interval, 0.21-1.00; P = .049). Hospitalized patients of Black race with COVID-19 were more prone to VTE development, and patients with COVID-19 who developed in-hospital VTE had roughly nearly threefold higher odds of mortality. Further emphasis should be placed on optimizing COVID-19 anticoagulation protocols to reduce mortality in this high-risk cohort.

Immune thrombocytopenia in 2 healthy young women after the Pfizer-BioNTech BNT16B2b2 messenger RNA coronavirus disease 2019 vaccination.

Immune thrombocytopenic purpura (ITP) is a rare complication associated with vaccines targeting various diseases, including influenza, measles-mumps-rubella, hepatitis B, and diphtheria-tetanus-pertussis. We report 2 cases of ITP in healthy 20-year-old and 21-year-old women presenting to Emory University in Atlanta, GA, 2 days after the second dose and 11 days after the first dose (respectively) of the Pfizer-BioNTech messenger RNA severe acute respiratory syndrome coronavirus 2 vaccine. Both patients recovered quickly. With more than a billion doses of coronavirus disease 2019 vaccines safely administered worldwide as of May 2021, discussions with patients should put into perspective the low risks of vaccination against the enormous societal benefit of the coronavirus disease 2019 vaccine.

Anticoagulation in cancer-associated thromboembolism with thrombocytopenia: a prospective, multicenter cohort study.

Venous thromboembolism (VTE) with concurrent thrombocytopenia is frequently encountered in patients with cancer. Therapeutic anticoagulation in the setting of thrombocytopenia is associated with a high risk of hemorrhage. Retrospective analyses suggest the utility of modified-dose anticoagulation in this population. To assess the incidence of hemorrhage or thrombosis according to anticoagulation strategy, we performed a prospective, multicenter, observational study. Patients with active malignancy, acute VTE, and concurrent thrombocytopenia (platelet count <100 000/µL) were enrolled. The cumulative incidences of hemorrhage or recurrent VTE were determined considering death as a competing risk. Primary outcomes were centrally adjudicated and comparisons made according to initial treatment with full-dose or modified-dose anticoagulation. A total of 121 patients were enrolled at 6 hospitals. Seventy-five patients were initially treated with full-dose anticoagulation (62%) and 33 (27%) with modified-dose anticoagulation; 13 (11%) patients received no anticoagulation. Most patients who received modified-dose anticoagulation had a hematologic malignancy (31 of 33 [94%]) and an acute deep vein thrombosis (28 of 33 [85%]). In patients who initially received full-dose anticoagulation, the cumulative incidence of major hemorrhage at 60 days was 12.8% (95% confidence interval [CI], 4.9-20.8) and 6.6% (95% CI, 2.4-15.7) in those who received modified-dose anticoagulation (Fine-Gray hazard ratio, 2.18; 95% CI, 1.21-3.93). The cumulative incidence of recurrent VTE at 60 days in patients who initially received full-dose anticoagulation was 5.6% (95% CI, 0.2-11) and 0% in patients who received modified-dose anticoagulation. In conclusion, modified-dose anticoagulation appears to be a safe alternative to therapeutic anticoagulation in patients with cancer who develop deep vein thrombosis in the setting of thrombocytopenia.

Fibrinolysis Shutdown and Thrombosis in a COVID-19 ICU.

ABSTRACT: The coronavirus disease (COVID-19) pandemic has threatened millions of lives worldwide with severe systemic inflammation, organ dysfunction, and thromboembolic disease. Within our institution, many critically ill COVID-19-positive patients suffered major thrombotic events, prompting our clinicians to evaluate hypercoagulability outside of traditional coagulation testing.We determined the prevalence of fibrinolysis shutdown via rotational thromboelastometry (ROTEM, Instrumentation Laboratories, Bedford, Mass) in patients admitted to the intensive care unit over a period of 3 weeks. In 25 patients who had a ROTEM test, we found that 11 (44%) met criteria for fibrinolysis shutdown. Eight of 9 (73%) of the VTE patients met criteria for fibrinolysis shutdown.Given the high rate of fibrinolysis shutdown in these patients, our data support using viscoelastic testing to evaluate for the presence of impaired fibrinolysis. This may help identify patient subsets who might benefit from the administration of fibrinolytics.

Treatment of catheter-related thrombosis in patients with hematologic malignancies: A Venous thromboEmbolism Network U.S. retrospective cohort study.

INTRODUCTION: Optimal treatment of catheter-related thrombosis (CRT) is uncertain in patients with hematologic malignancy. We aimed to evaluate the treatment strategies, outcomes, and predictors of recurrent venous thromboembolism (VTE) associated with catheter-related thrombosis (CRT) in patients with hematologic malignancy. METHODS: We performed a multicenter retrospective cohort study of eight institutions through the Venous thromboEmbolism Network US. Patients with hematologic malignancies with documented CRT were identified using ICD-9 and ICD-10 diagnostic codes. Semi-competing risks proportional hazard regression models were created. RESULTS AND CONCLUSIONS: Of the 663 patients in the cohort, 124 (19%) were treated with anticoagulation alone, 388 (58%) were treated with anticoagulation and catheter removal, 119 (18%) treated with catheter removal only, and 32 (5%) had neither catheter removal nor anticoagulation. 100 (15%) patients experienced a recurrent VTE event. In the 579 patients who had catheter removal, the most common reason for catheter removal was the CRT [392 (68%)]. For subjects who received any anticoagulation (n = 512), total anticoagulation duration was not associated with VTE recurrence [1.000 (0.999-1.002)]. After adjustment patients treated with catheter removal only had an increased risk of VTE recurrence [2.50 (1.24-5.07)] and death [4.96 (2.47-9.97)]. Patients with no treatment had increased risk of death [16.81 (6.22-45.38)] and death after VTE recurrence [27.29 (3.13-238.13)]. In this large, multicenter retrospective cohort, we found significant variability in the treatment of CRT in patients with hematologic malignancy. Treatment without anticoagulation was associated with recurrent VTE.