Major Thrombotic Complications Research Articles

Thrombotic events.

Major thrombotic complications in myeloproliferative neoplasms (MPNs) represent an important clinical problem due to their high morbidity, the complexity of their management, and their associated mortality. The appearance of a thrombosis implies a high thrombotic risk stratification of the MPN and determines the initiation or optimization of cytoreductive treatment and the use of antiplatelet or anticoagulant therapy as secondary prophylaxis. The incidence of thrombosis at the time of diagnosis is higher than during the course of the disease, being located in the arterial territory in 60-70% of cases. Once thrombosis has occurred, up to 20-33% of patients experience thrombotic recurrence in the same initial vascular territory.

Textbook Outcome for Superior Cavopulmonary Connection: A Metric for Single Ventricle Heart Surgery.

Background: To develop a more holistic measure of congenital heart center performance beyond mortality, we created a composite "textbook outcome" (TO) for the Glenn operation. We hypothesized that meeting TO would have a positive prognostic and financial impact. Methods: This was a single center retrospective study of patients undergoing superior cavopulmonary connection (bidirectional Glenn or Kawashima ± concomitant procedures) from 2005 to 2021. Textbook outcome was defined as freedom from operative mortality, reintervention, 30-day readmission, extracorporeal membrane oxygenation, major thrombotic complication, length of stay (LOS) >75th percentile (17d), and mechanical ventilation duration >75th percentile (2d). Multivariable logistic regression and Cox proportional hazards modeling were used. Results: Fifty-one percent (137/269) of patients met TO. Common reasons for TO failure were prolonged LOS (78/132, 59%) and ventilator duration (67/132, 51%). In multivariable analysis, higher weight [odds ratio, OR: 1.44 (95% confidence interval, CI: 1.15-1.84), P = .002] was a positive predictor of TO achievement while right ventricular dominance [OR 0.47 (0.27-0.81), P = .007] and higher preoperative pulmonary vascular resistance [OR 0.58 (0.40-0.82), P = .003] were negative predictors. After controlling for preoperative factors and excluding operative mortalities, TO achievement was independently associated with a decreased risk of death over long-term follow-up [hazard ratio: 0.50 (0.25-0.99), P = .049]. Textbook outcome achievement was also associated with lower direct cost of care [$137,626 (59,333-167,523) vs $262,299 (114,200-358,844), P < .0001]. Conclusion: Achievement of the Glenn TO is associated with long-term survival and lower costs and can be predicted by certain risk factors. As outcomes continue to improve within congenital heart surgery, operative mortality will become a less informative metric. Textbook outcome analysis may represent a more balanced measure of a successful outcome.

Abstract 12610: Outcomes of Patients With Cancer and Acute Myocardial Infarction-Associated Cardiogenic Shock Managed With Temporary Mechanical Circulatory Support

Introduction: Cardiogenic shock (CS) is a leading cause of in-hospital death among patients with acute myocardial infarction (AMI). Temporary mechanical circulatory support (tMCS) is used in AMI-CS and may improve end-organ perfusion at the risk of bleeding/thrombosis. Patients with cancer are at high risk of AMI and CS and are at risk of bleeding and thrombosis. However, there is limited data on the outcomes of patients with cancer and AMI-CS managed with tMCS. Methods: Adult patients with AMI-CS managed with tMCS from January 2006 to December 2018 with and without cancer were identified within the National Inpatient Sample. Propensity score matching (PSM) was performed to match 1 cancer patient to 10 non-cancer controls. Primary outcome was in-hospital death and secondary outcomes were major bleeding and thrombotic complications. Temporal trends of tMCS use in cancer patients were investigated. Results: Patient characteristics after PSM are described in Table. After PSM, 1,287 individuals with and 12,870 without cancer were included. Patient characteristics were well-balanced between cancer and non-cancer groups after PSM. After PSM, there was no difference in death (OR 1.00, 95% CI 0.88 - 1.13) or thrombotic complications (OR 1.10, 95% CI 0.91 - 1.34) between patients with and without cancer. Patients with cancer had higher risk of major bleeding (OR 1.29, 95% CI 1.15 - 1.46). Conclusions: Among patients hospitalized for AMI-CS managed with tMCS, cancer was associated with increased major bleeding but similar mortality and thrombotic risk. Future investigation is needed in order to further characterize and improve outcomes for this increasingly common patient population.

Essential Thrombocythemia: One-Center Data in a Changing Disease.

Introduction: Essential thrombocythemia is a chronic myeloproliferative neoplasm associated with thrombo-hemorrhagic events and the progression to myelofibrosis or acute myeloid leukemia. The purpose of this article is to present real-world data on ET cases diagnosed and managed between 1998 and 2020 in the largest, tertiary hematology reference center in Romania and to evaluate the impact of thrombotic events on survival. Methods: A real-world, retrospective cohort-type study was conducted. We collected and statistically analyzed data from 168 patients who met the 2016 WHO diagnostic criteria for ET and who were managed between 1998 and 2020 in our center. Results: The median age at diagnosis of ET was 51.8 years, with a female predominance (66.07%). The JAK2V617F mutation was detected in 60.71% of patients. Leukocytosis at diagnosis was associated with a higher risk of thrombosis, and JAK2V617F-positive cases exhibited a 1.5-fold higher risk of developing thrombotic events. The average survival in ET with major thrombosis was 14.5 years versus 20.6 years in ET cases without major thrombosis. Other predictors of survival were high-risk IPSET score and age >60 years. Conclusions: Romanian patients diagnosed with ET are generally younger than 60 years and are predominantly female. The occurrence of thrombotic events was influenced by gender, leukocyte count at diagnosis and JAK2V617F positivity. Survival was impacted by age, the presence of JAK2V617F mutation, hypertension, major thrombotic complications and IPSET score. Notably, these findings warrant careful interpretation and further confirmation in the setting of prospective studies.

Timing and safety of hip fracture surgery in patients on direct-acting oral anticoagulants

BackgroundMany geriatric patients presenting for emergency hip fracture surgery are on direct oral anticoagulants (DOACs) most of which are not easily reversible. A safe policy was required to reduce delays to surgery. Prior to institution of our hospital's protocol in January 2021, most of these patients had surgery after 48 h following the last dose of DOAC due to concerns about increased perioperative blood loss. MethodsThis was a prospective closed loop audit of the protocol-surgery within 24 h from last dose of DOAC (if creatinine clearance >50 ml/min) with administration of 1-g of tranexamic acid at anesthesia induction. 131 eligible patients (DOAC, n = 22; no anticoagulation, n = 109) between January–June 2021 who had emergency hip fracture surgery were identified. Primary outcome measures were peri-operative blood loss, transfusion requirements and policy compliance. Secondary outcome measures were 30-day mortality, thrombotic complications and wound bleeding. ResultsCompliance with surgical timing and tranexamic acid administration were 55% and 81% respectively after the second audit cycle. The mean estimated blood loss (EBL) in the DOAC group versus the non-anticoagulated control group was 500 ml and 330 ml respectively. The difference between these groups was statistically significant at an alpha level of 5% (P = 0.0115, 95% CI 38.48–299.16). The difference for intra-operative (RR 3.43; 95% CI 1.68–7.01) and post-operative blood transfusion (RR 2.10; 95% CI 1.23–3.58) for the 2 groups was also statistically significant. However, there was no case of massive blood transfusion in both groups. The DOAC group had a lower risk for 30-day mortality (RR 0.71; 95% CI 0.09-5.46). There was no major thrombotic complication in the DOAC group. ConclusionThis audit has shown that this protocol is safe although clinicians should anticipate some degree of increased intra-operative blood loss. We will recommend continuation of this policy with sustained safety monitoring in order to reduce delays to surgery.

Bleeding and thrombotic complications associated with anticoagulation prior to lung transplantation: a case series.

BackgroundScarce data is available on therapeutic anticoagulation (AC) in patients undergoing pulmonary transplantation. We describe our institutional experience with AC-induced coagulopathy in recipients at the time of transplantation and evaluate its impact on posttransplant outcomes.MethodsRecords of adult patients on therapeutic AC at the time of lung transplantation from January 2014 to July 2021 were reviewed. Administration of preoperative pharmacologic reversal was assessed, with adequate reversal defined as international normalized ratio (INR) ≤1.5. We evaluated the incidence of major bleeding complications [delayed sternal closure, reoperation due to bleeding, chest tube output ≥1,500 cc, ≥4 units of packed red blood cells, ≥4 units of platelets, or ≥5 units of fresh frozen plasma (FFP)], major thrombotic complications [venous thromboembolism (VTE) or other major thrombosis on imaging], and inpatient mortality.ResultsOf 602 lung transplant recipients, 10 patients taking preoperative warfarin were included in the study. While most patients received pharmacologic reversal preoperatively (n=9, 90%), successful reversal was rarely achieved (n=3, 30%). Inadequate INR reversal was associated with major bleeding events (n=6, 60%). Major thrombotic complications were more frequent (n=7, 70%) than bleeding events. Notably, all fatalities within the cohort (n=2, 20%) were associated with thrombotic, but not bleeding, complications.ConclusionsThis is the first known report on the incidence and impact of AC-induced coagulopathy in patients undergoing lung transplantation. Major thrombotic events are frequent and associated with high mortality. Routine surveillance and treatment may be warranted.

Patients prescribed antithrombotic medication in elective implant-based breast reconstruction are high risk for major thrombotic complications

Implant-based reconstruction (IBR) is the most frequently performed breast reconstruction procedure in the USA. As the US population ages, an increasing number of these patients suffer from comorbidities requiring the use of chronic antithrombotic therapy. Outcomes following IBR in patients prescribed these medications are not well understood. An all-payor administrative claims database (52 million patients) was queried for patients undergoing IBR from 2010 through 2018. Patients who were prescribed therapeutic antithrombotic therapy, and those who were not, were matched in a one-to-one fashion for comorbidities independently associated with bleeding and thrombo-ischemic events following first-stage IBR. Cox proportional hazards models investigated the 90-day risk of bleeding and major thrombo-ischemic events following IBR. Of the 36,379 patients found to have undergone IBR, 2,024 patients were perfectly matched for age and high-risk comorbidities. Patients prescribed antithrombotic drugs had increased 90-day risk for all thrombo-ischemic complications (HR: 5.62, 95% CI: 3.53-8.95, p < 0.0001), as well as a significantly increased risk for 90-day DVT, 90-day PE, 90-day myocardial infarction, and 90-day stroke. Patients specifically prescribed antiplatelet drugs, direct oral anticoagulants (DOAC), and warfarin had a significantly increased risk for transfusion. Patients prescribed antithrombotic therapy had a significantly increased risk for life-threatening thrombotic events and transfusion following elective IBR. This suggests a role for further monitoring and a potential role for multi- and interdisciplinary interventions to help mitigate this risk. These interventions can be the subject of future prospective studies.

Bivalirudin or Unfractionated Heparin for Anticoagulation in Pediatric Patients on Continuous Flow Ventricular Assist Device Support: Single-Center Retrospective Cohort Study

Bivalirudin is a direct thrombin inhibitor that is being increasingly used for anticoagulation in children after ventricular assist device (VAD) implantation. While the data on bivalirudin use in pulsatile flow VADs are growing, reports on its use in patients on continuous flow (CF) VAD as well as comparisons of associated outcomes with unfractionated heparin (UFH) remain limited. Retrospective cohort study. Single tertiary-quaternary referral center. All patients less than 21 years old on CF-VAD support who received bivalirudin or UFH for anticoagulation between the years 2016 and 2020. Not applicable. Clinical characteristics compared between the cohorts included time to target range of anticoagulation, markers of hemolysis, and prevalence of hemocompatibility-related adverse events such as major hemorrhagic complications, ischemic stroke, and pump thrombosis. In 42 unique patients (41 HeartWare HVAD [Medtronic, Minneapolis, MN], one HeartMate 3 LVAD [Abbott Laboratories, Abbott Park, IL]) during the study period, a total of 67 encounters of IV anticoagulation infusions (29 UFH and 38 bivalirudin) were retrospectively reviewed. In comparison with use of UFH, bivalirudin was associated with lesser odds of major bleeding complications (odds ratio [OR], 0.29; 95% CI, 0.09-0.97; p = 0.038). We failed to identify any difference in odds of major thrombotic complications (OR, 2.53; 95% CI, 0.47-13.59; p = 0.450). Eight of the patients (28%) on UFH were switched to bivalirudin due to hemorrhagic or thrombotic complications or inability to achieve therapeutic anticoagulation, while two of the patients (5%) on bivalirudin were switched to UFH due to hemorrhagic complications. Bivalirudin was used for a "washout" in eight cases with concern for pump thrombosis-six had resolution of the pump thrombosis, while two needed pump exchange. Use of bivalirudin for anticoagulation in patients on CF-VAD support was associated with lesser odds of hemorrhagic complications compared with use of UFH. Bivalirudin "washout" was successful in medical management of six of eight cases of possible pump thrombosis.

From pregnancy to SARS Cov II- pandemia. “Like a bridge over troubled waters” COVID 19: a new virus- induced thrombotic microangiopathy model? LDH/AST ratio diagnostic role

Several scientific studies have shown that SARS-CoV II infection, responsible for the COVID 19 pandemic, can lead to a state of thrombotic microangiopathy (TM), both thrombotic thrombocytopenic purpura-like (TTP-like) and atypical hemolytic-uremic syndrome-like (aHUS-like), similarly to what occurs in the major thrombotic complications of pregnancy. The differential diagnosis between these disorders is very complex, due to overlapping clinical features, and also because they affect various disciplines. In the context of thrombotic microangiopathies, the test for the evaluation of ADAMTS-13 plays a key role, but in the pending or absence of the ADAMTS-13 test we can use PLASMIC score and /or LDH/AST ratio and these can help in the early stages of the disease. TTP and aHUS have different treatments: plasmapheresis in the TTP and Eculizumab in the aHUS. Therefore, we propose to the scientific community the LDH / AST score as a diagnostic aid, to help the differential diagnosis between the SARS-CoV II associated-TM and direct towards a more specific and effective therapy, in Covid-19 critical Patients.

Thrombotic Events in Covid-19: Incidence and their Association with Lab Parameters, Vaccination Status and Mortality

Background &amp; Objectives: Major arterial or venous thrombotic complications occur frequently with COVID-19. This risk seems to be present despite no known underlying thrombophilia and even adequate anticoagulation does not diminish its risk. Whilst pulmonary embolism may seem to be the most common thrombotic complication, others may also occur. A vaccination link to thrombotic events in COVID-19 has not been studied to the best of our knowledge. Methods: In this retrospective cross-sectional study we determined the incidence of total thrombotic events, individual Venous Thromboembolisms (VTE) and Arterial Thromboembolisms (ATE) that occurred in patients requiring ICU admission for COVID-19 in one of Bahrain’s main COVID ICU facilities for a period of 6 months. We also aim to determine mortality rate in this group of patients, links with specific baseline characteristics, laboratory parameters and patient vaccination status. Results: We studied 1597 patients over 6 months, 6% of patients were found to have VTE or ATE with a cumulative incidence of 6.5% thrombotic events. Elevated D dimer &gt;1 was associated with an increased risk of thrombosis and an increased risk of mortality. There was a higher risk of thrombotic events in unvaccinated individuals. All-cause mortality in COVID-19 patients complicated with thrombosis and mortality solely secondary to thrombotic event were both significantly higher in unvaccinated individuals. Conclusions: Based on the findings of this study, unvaccinated individuals are at significantly higher risk of developing thrombotic events. This will assist in enabling physicians to lower their threshold of diagnosing such events. The urgency of lab parameters the swift management of other risk factors and the importance of vaccination against COVID-19 can be further studied. Keywords: COVID-19, Venous Thromboembolisms, Arterial Thromboembolisms, Mortality, D dimer, Vaccination status

Vena Cava Thrombosis after Congenital Diaphragmatic Hernia Repair: Multivariate Analysis of Potential Risk Factors.

The treatment of newborns with congenital diaphragmatic hernia (CDH) is associated with a significant complication rate. Information on major thrombotic complications and their incidence in newborns with CDH is lacking. The aims of our analysis were to evaluate the frequency of vena cava thrombosis and to determine its predictors within a consecutive series of patients with CDH. We retrospectively analyzed charts of all neonates of our department that underwent CDH repair from 2007 to 2021, focusing on vena cava thrombosis. Vena cava thrombosis was diagnosed sonographically and classified as complete or partial venous occlusion. Complete occlusion was confirmed by cavography. Variables evaluated were CDH side, liver position, central vein line, surgical approach, and extracorporeal membrane oxygenation (ECMO). Univariate and multivariate tests were utilized. Among 57 neonates who underwent CDH repair, vena cava thrombosis was diagnosed in 14 (24.6%), seven of whom had complete occlusion of the vena cava. Factors associated with vena cava thrombosis were femoral or saphenous venous catheter (p = 0.044), right sided CDH (p = 0.027) and chylothorax (p < 0.0001). ECMO was not associated with vena cava thrombosis. Seven patients (50%) with vena cava thrombosis were treated interventionally with angioplasty and seven (50%) conservatively with anticoagulation only. Mortality was not higher in patients with compared with patients without vena cava thrombosis. The incidence of vena cava thrombosis in newborns with CDH in our series is high. Routine postoperative abdominal sonography focusing on vena cava thrombosis is mandatory in all patients with CDH. Patients who developed vena cava thrombosis were more likely to develop chylothorax after CDH repair. Considering the good outcome of medical therapy of partial vena cava thrombosis, it may be discussed whether low dose anticoagulation may be provided to all newborns with CDH.

Clopidogrel Loading Dose 300 vs. 600 mg in Patients Undergoing One-Stop Hybrid Coronary Revascularization: A Prospective Single-Center Randomized Pilot Study.

Background: The optimal loading dose of clopidogrel in one-stop hybrid coronary revascularization (HCR) remains an “evidence-free” zone. This study aimed to compare the major bleeding and ischemic thrombotic events between different clopidogrel loading doses (300 vs. 600 mg) in one-stop HCR.Methods: In this prospective, single-center, randomized, and parallel pilot study, 100 patients receiving one-stop HCR were randomly assigned to the clopidogrel loading dose 300-mg group or 600-mg group in a 1:1 ratio. Major bleeding events and composite in-hospital ischemic thrombotic and adverse complications were evaluated after the procedure.Results: The results showed that postoperative mean chest drainage of the first 4 days and total drainage were comparable between the two groups. No differences were found in Bleeding Academic Research Consortium (BARC) coronary artery bypass grafting (CABG) related bleeding (4 vs. 2%, P = 1), PLATelet inhibition and patient Outcomes (PLATO) life-threatening bleeding (20 vs. 26%, P = 0.48), and PLATO major bleeding (70 vs. 76%, P = 0.5) in the two groups. The composite ischemic thrombotic and adverse events were also similar.Conclusions: In patients receiving one-stop HCR, clopidogrel 600 mg loading dose did not increase major bleeding events compared with 300 mg. More sufficient data is necessary to evaluate the potential benefits of 600 mg loading dose in one-stop HCR.

Recombinant Factor VIIa in Pediatric Cardiac Surgery

ObjectivesRecombinant activated factor VIIa (rVIIa) is used off-label for refractory bleeding after cardiac surgery. This study reviewed the indications, usage rates, and complications of rVIIa. DesignA retrospective case-control observational study. SettingA single quaternary pediatric hospital. ParticipantsAll children undergoing cardiac surgery with cardiopulmonary bypass over a three-year period. InterventionsAdministration of rVIIa as rescue therapy for refractory bleeding after weaning from cardiopulmonary bypass. Measurements and Main ResultsOnethousand, five hundred fifteen cardiopulmonary bypass procedures were reviewed. Patients receiving rVIIa were each matched to two control patients by age, procedure type, and bypass time. Data collected included weight, crossclamp time, anticoagulant and antifibrinolytic dose, return to the operating room for bleeding, thrombotic events, and extracorporeal membrane oxygenation (ECMO) circuit interventions.Forty-two patients received rVIIa (2.8%). Major systemic thrombotic complications were observed in 19% (controls 12.5%) of patients; 80% of recombinant factor VIIa patients requiring postoperative ECMO had interventions for circuit thrombosis (controls 31.25%); 4.76% of rVIIa recipients required reexploration for intractable bleeding (controls 1.39%). ConclusionsThis study added to understanding regarding the use of recombinant factor VIIa in pediatric cardiac surgery and reported increased thrombotic complications, especially for children who progress to ECMO. Prospective studies to better understand the pathophysiology of coagulopathy and hemorrhage in pediatric cardiac surgery and the role of hemostatic agents, such as rVIIa, are required.

The hemostatic and thrombotic complications of liver disease.

Hepatic cirrhosis leads to numerous hematologic derangements resulting in a complex and tenuously rebalanced hemostatic milieu. The utility of common hematologic tests including the INR and aPTT in assessing hemostatic and thrombotic risk in patients with cirrhosis is limited, and consensus on transfusion thresholds and proper management of thrombotic complications continues to evolve. This review summarizes the pathophysiology of key derangements of hemostasis including those of platelets, von Willebrand factor, pro- and anticoagulation factors, and fibrin. Additionally, the pathogenesis, consequences, optimal management, and prevention of major thrombotic and bleeding complications in cirrhosis arte discussed.

Context-Responsive Anticoagulation Reduces Complications in Pediatric Extracorporeal Membrane Oxygenation.

Purpose: We sought to determine the impact of a comprehensive, context-responsive anticoagulation and transfusion guideline on bleeding and thrombotic complication rates and blood product utilization during extracorporeal membrane oxygenation (ECMO).Design: Single-center, observational pre- and post-implementation cohort study.Setting: Academic pediatric hospital.Patients: Patients in the PICU, CICU, and NICU receiving ECMO support.Interventions: Program-wide implementation of a context-responsive anticoagulation and transfusion guideline.Measurements: Pre-implementation subjects consisted of all patients receiving ECMO between January 1 and December 31, 2012, and underwent retrospective chart review. Post-implementation subjects consisted of all ECMO patients between September 1, 2013, and December 31, 2014, and underwent prospective data collection. Data collection included standard demographic and admission data, ECMO technical specifications, non-ECMO therapies, coagulation parameters, and blood product administration. A novel grading scale was used to define hemorrhagic complications (major, intermediate, and minor) and major thromboembolic complications.Main Results: Seventy-six ECMO patients were identified: 31 during the pre-implementation period and 45 in the post-implementation period. The overall observed mortality was 33% with no difference between groups. Compared to pre-implementation, the post-implementation group experienced fewer major hemorrhagic and major thrombotic complications and less severe hemorrhagic complications and received less RBC transfusion volume per kg.Conclusions: Use of a context-responsive anticoagulation and transfusion guideline was associated with a reduction in hemorrhagic and thrombotic complications and reduced RBC transfusion requirements. Further evaluation of guideline content, compliance, performance, and sustainability is needed.

Increased Intracranial Hemorrhage Amid Elevated Inflammatory Markers in Those With COVID-19 Supported With Extracorporeal Membrane Oxygenation.

COVID-19-related coagulopathy is a known complication of SARS-CoV-2 infection and can lead to intracranial hemorrhage (ICH), one of the most feared complications of extracorporeal membrane oxygenation (ECMO). We sought to evaluate the incidence and etiology of ICH in patients with COVID-19 requiring ECMO. Patients at two academic medical centers with COVID-19 who required venovenous-ECMO support for acute respiratory distress syndrome (ARDS) were evaluated retrospectively. During the study period, 33 patients required ECMO support; 16 (48.5%) were discharged alive, 13 died (39.4%), and 4 (12.1%) had ongoing care. Eleven patients had ICH (33.3%). All ICH events occurred in patients who received intravenous anticoagulation. The ICH group had higher C-reactive protein (P = 0.04), procalcitonin levels (P = 0.02), and IL-6 levels (P = 0.05), lower blood pH before and after ECMO (P < 0.01), and higher activated partial thromboplastin times throughout the hospital stay (P < 0.0001). ICH-free survival was lower in COVID-19 patients than in patients on ECMO for ARDS caused by other viruses (49% vs. 79%, P = 0.02). In conclusion, patients with COVID-19 can be successfully bridged to recovery using ECMO but may suffer higher rates of ICH compared to those with other viral respiratory infections.

Abstract 17265: Prognostic Value of Serial D-dimers in Severe COVID-19 Infections

Introduction: COVID-19 infection causes a thrombotic state and elevation in D-dimer. This study characterizes the contour and nature of D-dimer elevation during severe COVID-19 infections. Methods: Retrospective review of 100 consecutive COVID-19 patients selected for severe infection at a tertiary medical center in New York City admitted to four COVID units and three ICU units on 04/15/2020. Admission D-dimer and serial D-dimer values during hospitalization were obtained as were demographic data, major thrombotic complications, and other significant hospital events. Data was analyzed with the Mann-Whitney U test, student’s t-test, and chi-squared test. Results: Hospital mortality was 28% among these 100 study subjects, ventilatory support 47%, ICU stay 40%, discharged in 61% and 11% remained hospitalized on 5/15/2020. Admission D-dimer elevated in 89% (mean D-dimer 3.36+/-4.84 mg/L) and 97% of hospitalized patients had elevated D-dimer (peaked mean D-dimer 7.33+/-7.34 mg/L). There was no significant difference in the admission D-dimers between patients who died versus those who survived (3.50+/-0.81 vs 3.02+/-0.55 mg/L, p=0.19), however; the contours of the subsequent D-dimers were significantly different between those who died versus survivors. Mean in hospital D-dimer remained without significant change in the survivor group but increased significantly in the deceased group (3.06+/-0.53 vs 4.62+/-0.48 mg/L, p&lt;0.001). The final D-dimer measurement prior to a patients discharge or death was significantly higher in the deceased group vs the survivor group (5.53+/-0.86 vs 1.98+/-0.39 mg/L, p&lt;0.001). There were 27 thrombotic complications (CVA 10, MI 4, PE 6, DVT 5, arterial thrombosis 2) diagnosed in 22 patients. Elevated peaked D-dimers were significantly associated with ICU (12.04 +/-6.96 mg/L, R 0.27-20, 95% CI 2.23) vs. no-ICU stay (5.13 +/- 6.49 mg/L, R 0.3-20, 95% CI 1.68, p&lt;0.001), and thrombotic complications (12.60 +/- 7.62 mg/L, R 0.27-20, 95% CI 3.38) vs. no thrombotic complication (6.57 mg/L +/- 0.3-20, 95% CI 1.47, p&lt;0.001). Conclusions: D-dimers were near universally elevated in severe COVID-19 infection but a marked upward trending of D-dimers presaged COVID-associated complications and a poor outcome.

Clinical & Economic Implications of Hydroxyurea Intolerance in Polycythemia Vera in Routine Clinical Practice in Israel

Background: Hydroxyurea (HU) is an effective and common therapy for high-risk Polycythemia Vera (PV). Some patients may demonstrate resistance or intolerance to HU, but the consequences of these warrant further studies. Objective: Evaluate the clinical and economic implications of HU resistance/intolerance, in routine clinical practice in Israel. Methods: A retrospective analysis of Maccabi Health Services' (MHS) database was performed. MHS is a Non-for-Profit healthcare insurer and provider in Israel, with over 2.2 million members. Patients were included in the study if they had a recorded PV diagnosis or complete blood count indicative of PV, and had purchased HU for at least 3 months between 2000-2015. Enrolled patients were divided into 3 groups: A) Resistant to HU (patients prescribed 2g/day of HU); B) Intolerant of HU (patients who stopped HU, transitioned to another line of therapy or who developed HU related cytopenias); C) Stable on HU. A mid-time point was added to "Stable" to compensate for the time required for transition in the "Intolerant" group. Only patients who developed Intolerance within 5 years were included. Collected data pertained to demographics, clinical outcomes, resource utilization and expenditure data. Results: A total of 830 patients were identified. Only 3 met criteria for Resistance and were disregarded for further analysis, while 318 (38%) were defined as "Intolerant" and 509 (61%) as "Stable". At baseline, there were no significant differences between "Intolerant" and "Stable" groups, apart from platelet counts (431 vs. 495, respectively) and red cell distribution width (RDW) (18.4 vs. 17.6, respectively). Intolerance was determined based on HU-related cytopenias (n=144, 45% of Intolerant), transition to other treatment line (n=52, 16%) or stopping HU (n=122, 38%). These results indicate some patients continue HU treatment despite lack of disease control. "Intolerant" patients who had transitioned by 5 years from first HU purchase (N=173) and "Stable" patients who met the mid-point of time to transition (N=487) were eligible for comparison. Median follow up time was 4.9 and 5.5 years for "Intolerant" and "Stable" groups, respectively. Thrombotic events occurred in 8% of the "Intolerant" group compared with 3% of "Stable" (p=0.003) and event rate per 100 patient-years was 1.6 versus 0.5 (p&amp;lt;0.001). Progression to MF occurred in 28% versus 5% (p&amp;lt;0.001), and progression to AML occurred in 6% compared with 1% (p&amp;lt;0.001) among "Intolerant" and "Stable", respectively. Interestingly no significant difference was found regarding major arterial thrombotic complications, (myocardial infarction, acute coronary syndrome, cerebrovascular accident or limb ischemia). During study follow up, hospitalization occurred in 84% versus 69% (p&amp;lt;0.001), and hospitalization days were 5.3 vs 1.9 per year (p=0.004) among "Intolerant" and "Stable" groups, respectively. Death occurred in 58% of "Intolerant" compared with 30% of "Stable"(p&amp;lt;0.001). Treatment costs for an Intolerant patient in the first year after intolerance were 2.6-fold higher than those for a Stable patient, driven mainly by hospitalization costs being 3.6-fold higher (data available from 2010). Conclusions: The results of this analysis indicate that intolerance to HU treatment in PV patients is associated with serious clinical and economic implications, indicating a need for improved treatment for these patients. Disclosures Ellis: Novartis Pharma AG: Consultancy, Honoraria, Other: Institutional research grant; BMS: Consultancy, Other: Institutional research grant; Gilead: Other: Institutional research grant. Tadmor:AbbVie: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Sanofi: Consultancy, Speakers Bureau; Medison: Consultancy, Speakers Bureau; Neopharm: Consultancy, Speakers Bureau; 6. Novartis Israel Ltd., a company wholly owned by Novartis Pharma AG: Consultancy, Speakers Bureau. Chodick:Novartis Pharma AG: Other: Institutional grant. Yekutiel:Novartis Israel Ltd., a company wholly owned by Novartis Pharma AG: Other: Institutional grant. Sharf:Novartis Pharma AG: Consultancy, Other: Institutional Grant; Leukaemia Patient Advocates Foundation: Ended employment in the past 24 months, Membership on an entity's Board of Directors or advisory committees; Israeli CML Patient Organisation: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Other: Institutional grant; AbbVie: Consultancy, Other: Institutional Grant; Amgen: Consultancy, Other: Institutional grant; Bristol Mayers Squibb: Consultancy, Other: Institutional Grant; Celgene: Consultancy, Other: Institutional Grant; AOP Orphan: Other: Institutional grant; CTI: Other: Institutional grant; Medison: Other; Roche: Other; Jansseb: Other; Pfizer: Consultancy, Other; Takeda: Other; Gilead: Other. Feine:Novartis Israel Ltd., a company wholly owned by Novartis Pharma AG: Current Employment. Leef:Novartis Israel Ltd., a company wholly owned by Novartis Pharma AG: Current Employment. Ben Zvi:Novartis Israel Ltd., a company wholly owned by Novartis Pharma AG: Current Employment. Shavit:6. Novartis Israel Ltd., a company wholly owned by Novartis Pharma AG: Current Employment.

In-home Compared With In-Clinic Warfarin Therapy Monitoring in Mechanical Heart Valves: A Population-Based Study.

ObjectiveTo evaluate differences in time in therapeutic range (TTR), major bleeding, thromboembolism, and survival comparing in-home and in-clinic international normalized ratio monitoring for patients with mechanical heart valves receiving warfarin anticoagulation.Patients and MethodsAn observational population-based study of 383 patients (mean ± SD age, 61.5±14.1 years; 38.6% female) with mechanical heart valves (aortic, 77.8%; mitral, 31.1%; tricuspid, 1%; pulmonic 0.2%; and multiple, 9.7%) was performed from January 1, 2012, through December 31, 2017. The target international normalized ratio was 2.5 for 199 patients (52.0%) and 3.0 for 184 (48.0). Of these patients, 37.9% (n=145) were managed by in-home monitoring (cases) and 62.1% (n=238) were monitored in the clinic (controls).ResultsDuring median follow-up of 3.1 years, mean ± SD TTR was similar between in-home (66.6%±19.2%) and in-clinic (67.2%±19.8%) monitoring (P=.76). There were no differences between the in-home and in-clinic groups regarding survival to major bleeding (5.7% per person-year vs 6.7% per person-year; P=.66) or thrombotic complications (2.3% vs 1.8%; P=.56). In-home monitoring was associated with reduced all-cause mortality (hazard ratio, 0.40; 95% CI, 0.19 to 0.83; P=.01) on univariate analysis; however, this was no longer apparent when controlling for age and baseline left ventricular ejection fraction.ConclusionIn this real-world population-based study of patients with mechanical heart valves, in-home monitoring was equivalent to in-clinic monitoring regarding TTR and important clinical outcomes.

Thrombopoietin Contributes to Extreme Thrombocytosis After Pediatric Pancreatectomy With Islet Autotransplantation.

This study aims to explore the role of thrombopoietin (TPO) production in extreme thrombocytosis that is often observed after pancreatectomy with islet autotransplantation (IAT) and the effectiveness of hydroxyurea in thrombocytosis management. Retrospective chart review was performed for all patients who underwent pancreatectomy with IAT at our institution between April 1, 2015, and December 31, 2016. Data evaluated included demographics, platelet counts, TPO levels, and thrombocytosis management strategies. Twelve total and 1 subtotal pancreatectomy with IAT cases were reviewed. All operations included splenectomy. No major surgical or thrombotic complications occurred. Thrombopoietin levels, normal preoperatively, rose significantly (median, 219 pg/mL) soon after surgery, peaking on median postoperative day 3. Platelet counts, also normal preoperatively, increased within a week of surgery, with 92% over 1000 K/μL (median peak platelet count, 1403 K/μL). Platelet counts and TPO levels dropped after hydroxyurea initiation in most patients. After pancreatectomy with IAT, patients experienced marked TPO rise and subsequent thrombocytosis, and both decreased significantly after hydroxyurea initiation. These data suggest that TPO elevation and associated increased platelet production may be one driver of early extreme post-total pancreatectomy with islet autotransplantation thrombocytosis, and this process may be modulated by hydroxyurea.