The standard of care for the treatment of cancer-related venous thromboembolism (VTE) is a low molecular weight heparin (LMWH) formulation. The recent development of direct oral anticoagulants ...(DOACs) and their approval for the treatment of VTE has resulted in several new options for treatment. If equivalent to LMWH in terms of safety and effectiveness, the use of DOACs in the treatment of cancer-related VTE would reduce the risk of VTE recurrence while potentially improving the quality of life of many cancer patients.
We performed a retrospective analysis of adult patients with cancer-related VTE treated in our benign hematology clinic. Among the 153 patients included in our final analysis, 123 (80%) were treated with LMWH and 30 (20%) were treated with DOACs. Patients had 36 different histological types of cancer. The primary outcome was the rate of recurrence of VTE evaluated at 6 and 12months after the initiation of anticoagulation. Secondary outcomes were the rate of anticoagulant-associated clinically relevant bleeding and event-free survival for VTE recurrence.
In comparing the 2 treatment groups, there was no statistically significant difference in the cumulative rates of VTE recurrence at 6 and 12months or in the rates of major or non-major bleeding at both 6 and 12months. The median VTE recurrence-free survival rates were not reached and they were not statistically different.
DOACs appear to be as safe and effective as conventional therapy for the treatment of cancer-related VTE. Results of ongoing randomized clinical studies may provide definitive evidence and clarify the role of the DOACs in the setting of malignancy.
Abstract
Background
Patients with gastrointestinal cancer (GICA) are at high risk for venous thromboembolism (VTE). Data from randomized clinical trials in cancer-associated VTE suggest that direct ...oral anticoagulants (DOACs) conferred similar or superior efficacy but a heterogeneous safety profile in patients with GICA. We compared the safety and effectiveness of DOACs in patients with GICA and VTE at MD Anderson Cancer Center.
Materials and Methods
This was a retrospective chart review of patients with GICA and VTE receiving treatment with DOACs for a minimum of 6 months. Primary outcomes were the proportion of patients experiencing major bleeding (MB), clinically relevant non-major bleeding (CRNMB), and recurrent VTE. Secondary outcomes were time to bleeding and recurrent VTE.
Results
A cohort of 433 patients with GICA who were prescribed apixaban (n = 300), or rivaroxaban (n = 133) were included. MB occurred in 3.7% (95% confidence interval CI 2.1-5.9), CRNMB in 5.3% (95% CI 3.4-7.9), and recurrent VTE in 7.4% (95% CI 5.1-10.3). The cumulative incidence rates of CRNMB and recurrent VTE were not significantly different when comparing apixaban to rivaroxaban.
Conclusion
Apixaban and rivaroxaban had a similar risk of recurrent VTE and bleeding and could be considered as anticoagulant options in selected patients with GICA and VTE.
Patients with cancer are at increased risk for venous thromboembolism. This article evaluates the safety and effectiveness of direct oral anticoagulants in patients with gastrointestinal cancer and cancer-associated venous thromboembolism.
Venous thromboembolism (VTE) and stroke carry significant mortality and morbidity in cancer patients. Direct oral anticoagulants (DOACs) have been demonstrated to be effective for the treatment of ...VTE and prevention of stroke in atrial fibrillation (AF). Bleeding rates are variable and are based on the cancer type and the patient’s specific risk factors. There are approved specific antidotes for DOAC-associated bleeding. Other strategies are available for bleeding reversal, including the use of prothrombin complex concentrate (PCC). No randomized studies have compared head-to-head the efficacy and safety of reversal agents. We aim to examine the safety and effectiveness of hemostatic agents in cancer patients with DOAC-related major bleeding. A retrospective chart review study of patients at MD Anderson Cancer Center with DOAC-related major bleeding between 2014 and 2019. Bleeding severity and clinical hemostasis were described based on ISTH guidelines and the Sarode criteria, respectively. The rates of thrombotic complications and mortality at 30-day from the index bleeding event were described. We identified 23 patients with DOAC-related major bleeding; 14 patients received PCC and 9 patients received andexanet alfa. The most common sites of bleeding were the gastrointestinal tract and intracranial. Effective hemostasis and 30-day mortality were similar to reported results from other reports of outcomes of reversal agents for DOAC related-bleeding in non-cancer patients. One patient in each treatment group experienced a thrombotic event. Further larger scale studies are needed to confirm our findings in cancer patients.
Patients undergoing allogenic hematopoietic stem cell transplantation (allo-HSCT) require indwelling central venous catheters. The comparative incidence, risk, and outcome of isolated ...catheter-related deep venous thrombosis (CR-DVT) versus pulmonary embolism/lower-extremity DVT (PE/LE-DVT) remains unclear.
We conducted a retrospective cohort study for patients undergoing allo-HSCT from 2006 to 2019. CR-DVT and PE/LE-DVT outcomes were screened using ICD codes and radiology reports and confirmed by medical record reviews. Cox regression models were used to assess the association between thrombotic outcomes and pertinent baseline and time-varying covariates. The impact of thrombotic events within 1-year post-transplant (time-varying) on overall mortality was also assessed.
Among 2879 patients, the cumulative incidence of isolated CR-DVT and PE/LE-DVT at 12 months was 4.2 % and 4.8 %, respectively. The strongest time-varying predictor for onset of CR-DVT and PE/LE-DVT was hospitalization inpatient status (HR 3.71 95 % CI 2.16–6.37 and 3.99 95 % CI 2.00–7.99, respectively). Other overlapping variables included lymphoma diagnosis and BMI > 35 kg/m2, whereas acute GVHD grades 2–4 were found to be significantly associated with risk of PE/LE-DVT but not CR-DVT. After adjusting for baseline variables and acute GVHD, the occurrences of CR-DVT and PE/LE-DVT were both independently associated with increased overall mortality (HR 1.58 95 % CI 1.23–2.02 and HR 1.53 95 % CI 1.19–1.97, respectively).
We observed a high incidence of both CR-DVT and PE/LE-DVT with overlapping and unique risk factors. CR-DVT was also associated with increased mortality similar to PE/LE-DVT. Standardized strategies targeting high-risk hospitalization periods may help mitigate the development of thrombotic outcomes post-transplant.
•Catheter related thrombosis is a common complication in stem cell transplant.•The 12-month cumulative incidence of catheter related thrombosis was 4.2 %.•Isolated catheter related thrombosis was associated with increased mortality.•Inpatient status, lymphoma, and body mass index were predictive of thrombosis.•Graft versus host disease was only predictive of non-catheter related thrombosis.
Erythrocytosis is associated with an elevation of the hemoglobin level above 16.5 g/dL in men and above 16 g/dL in women and an elevation of the hematocrit level above 49% in men and > 48% in women. ...In primary erythrocytosis, the defect is a clonal disorder in the myeloid compartment of the bone marrow, leading to an increased red cell production. Secondary erythrocytosis is the result of external stimuli to the bone marrow, leading to the production of red cells in excess. Secondary erythrocytosis is more common than primary erythrocytosis and has a broad differential diagnosis.
This review will discuss secondary erythrocytosis, its causes, clinical presentation, and both diagnostic and therapeutic approaches.
Although secondary erythrocytosis is more common than PV, there are still challenges and difficulties associated with the distinction between these two conditions. Moreover, there is a paucity of data and guidance when it comes to the management of certain congenital and acquired conditions. A pragmatic approach is recommended in order to identify the cause for this condition. Treatment should be directed at the management of the underlying cause.
Venous thromboembolism (VTE) is a significant complication for cancer patients undergoing systemic therapy. We performed an independent external validation for a recently derived and validated a ...novel electronic health record (EHR) VTE risk score in a comprehensive cancer center. Adult patients with incident cancer diagnoses were identified from MD Anderson Cancer Center Tumor Registry 1/2017-1/2021. Baseline covariates extracted at the time of first-line systemic therapy included demographics, cancer site/histology, stage, treatment, complete blood count, body mass index, recent prolonged hospitalization, and history of VTE or paralysis. VTE was ascertained using an institution-specific natural language processing radiology algorithm (positive predictive value of 94.8%). The median follow-up for 21 142 cancer patients was 8.1 months. There were 1067 (5.7%) VTE within 6 months after systemic therapy. The distribution of the novel score for 0-, 1, 2, 3, 4, 5+ was 5661, 3558, 3462, 3489, 2918, and 2054; while the corresponding 6-month VTE incidence was 1.3%, 3.1%, 5.4%, 7.3%, 9.3%, and 13.8%, respectively (c statistic 0.71 95% CI 0.69-0.72 with excellent calibration). In comparison, the Khorana score had a c statistic of 0.64 95% CI 0.62-0.65. The two risk scores had 80% concordance; the novel score reclassified 20% of Khorana score (3530 low-to-high with 9.0% VTE; 734 high-to-low with 3.4% VTE) and led to a 25% increment in VTEs captured in the high-risk group. In conclusion, the novel score demonstrated consistent discrimination and calibration across cohorts with heterogenous demographics. It could become a new standard to select high-risk populations for clinical trials and VTE monitoring.
Red cell overproduction is seen in polycythemia vera (PV), a bone marrow myeloproliferative neoplasm characterized by trilinear cell proliferation (WBC, platelets), as well as in secondary ...erythrocytosis (SE), a group of heterogeneous disorders characterized by elevated EPO gene transcription. We aimed to verify the concordance of the International Classification of Diseases (ICD) code-based diagnosis of "polycythemia" or "erythrocytosis" with the true clinical diagnosis of these conditions. We retrospectively reviewed the electronic medical records (January 1, 2005, to December 31, 2016) of adult patients with ICD codes of polycythemia and/or erythrocytosis who had testing done for the presence of the JAK2V617F mutation. We verified the accuracy of the ICD code-based diagnoses by meticulous chart review and established whether these patients fulfilled the criteria by the evaluating physician for PV or SE and according to the World Health Organization 2016 diagnostic guidelines. The reliability of ICD coding was calculated using Cohen's kappa. We identified and chart reviewed a total of 578 patient records. Remarkably, 11% of the patients had concurrent diagnosis codes for PV and SE and were unable to be classified appropriately without individual chart review. The ICD code-based diagnostic system led to misidentification in an important fraction of cases. This represents a problem for the detection of PV or SE cases by ICD-based registries and their derived studies. Research based exclusively on ICD codes could have a potential impact on patient care and public health, and limitations must be weighed when research findings are conveyed.
Venous thromboembolism (VTE) poses a significant risk to cancer patients receiving systemic therapy. The generalizability of pan-cancer models to lymphomas is limited. Currently, there are no ...reliable risk prediction models for thrombosis in patients with lymphoma. Our objective was to create a risk assessment model (RAM) specifically for lymphomas. We performed a retrospective cohort study to develop Fine and Gray sub-distribution hazard model for VTE and pulmonary embolism (PE)/ lower extremity deep vein thrombosis (LE-DVT) respectively in adult lymphoma patients from the Veterans Affairs national healthcare system (VA). External validations were performed at the Harris Health System (HHS) and the MD Anderson Cancer Center (MDACC). Time-dependent c-statistic and calibration curves were used to assess discrimination and fit. There were 10,313 (VA), 854 (HHS), and 1858 (MDACC) patients in the derivation and validation cohorts with diverse baseline. At 6 months, the VTE incidence was 5.8% (VA), 8.2% (HHS), and 8.8% (MDACC), respectively. The corresponding estimates for PE/LE-DVT were 3.9% (VA), 4.5% (HHS), and 3.7% (MDACC), respectively. The variables in the final RAM included lymphoma histology, body mass index, therapy type, recent hospitalization, history of VTE, history of paralysis/immobilization, and time to treatment initiation. The RAM had c-statistics of 0.68 in the derivation and 0.69 and 0.72 in the two external validation cohorts. The two models achieved a clear differentiation in risk stratification in each cohort. Our findings suggest that easy-to-implement, clinical-based model could be used to predict personalized VTE risk for lymphoma patients.
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