A novel model for predicting hospitalization risk among hemodialysis patients based on blood test variables.

Hemodialysis patients are at high risk of hospitalization. Predicting such risk in dialysis patients may be critical to maintaining quality of life and reducing costs to the healthcare system. In this paper, we present and fractional polynomial stepwise logistic regression model to specify how routinely collected blood test variables could be linked to a significant increase in hospitalization risk. We found that eight of nineteen variables were significantly able to predict hospitalization risk; albumin (p<0.05), creatinine (p<0.05), calcium (p<0.01), bicarbonate (p<0.01), hemoglobin (p<0.05), mean cell hemoglobin concentration (MCHC) (p<0.0001), mean corpuscular volume (MCV) (p<0.0001), and potassium (p<0.01). The model achieved accuracy, sensitivity, and specificity of 77.31%, 83.03%, and 69.05%, respectively.

Thrombosis risk associated with COVID-19 infection. A scoping review.

BACKGROUND: Infection by the 2019 novel coronavirus (COVID-19) has been reportedly associated with a high risk of thrombotic complications. So far information is scarce and rapidly emerging. METHODS: We conducted a scoping review using a single engine search for studies assessing thrombosis and coagulopathy in COVID-19 patients. Additional studies were identified by secondary review and alert services. RESULTS: Studies reported the occurrence of venous thromboembolism and stroke in approximately 20% and 3% of patients, respectively. A higher frequency seems to be present in severely ill patients, in particular those admitted to intensive care units. The thrombotic risk is elevated despite the use of anticoagulant prophylaxis but optimal doses of anticoagulation are not yet defined. Although an increase of biomarkers such as D-dimer has been consistently reported in severely ill COVID-19, the optimal cut-off level and prognostic value are not known. DISCUSSION: A number of pressing issues were identified by this review, including defining the true incidence of VTE in COVID patients, developing algorithms to identify those susceptible to develop thrombotic complications and severe disease, determining the role of biomarkers and/or scoring systems to stratify patients' risk, designing adequate and feasible diagnostic protocols for PE, establishing the optimal thromboprophylaxis strategy, and developing uniform diagnostic and reporting criteria.

Development of a Clinical Prediction Rule for Venous Thromboembolism in Patients with Acute Leukemia.

Risk factors for venous thromboembolism in patients with solid tumors are well studied; however, studies in patients with acute leukemia are lacking. We conducted a retrospective cohort study of adult patients diagnosed with acute myeloid leukemia and acute lymphoblastic leukemia diagnosed between June 2006 and June 2017 at a tertiary care center in Canada. Potential predictors of venous thromboembolism were evaluated using logistic regression and a risk score was derived based on weighed variables and compared using survival analysis. Internal validation was conducted using nonparametric bootstrapping. A total of 501 leukemia patients (427 myeloid and 74 lymphoblastic) were included. Venous thromboembolism occurred in 77(15.3%) patients with 71 events occurring in the first year. A prediction score was derived and validated and it included: previous history of venous thromboembolism (3 points), lymphoblastic leukemia (2 points), and platelet count > 50 × 109/L at the time of diagnosis (1 point). The overall cumulative incidence of venous thromboembolism was 44% in the high-risk group (≥ 3 points) versus 10.5% in the low-risk group (0-2 points) and it was consistent at different follow-up periods (log-rank p < 0.001). We derived and internally validated a predictive score of venous thromboembolism risk in acute leukemia patients.

Treatment of venous thromboembolism in acute leukemia: A systematic review.

BACKGROUND: The safety and efficacy of venous thromboembolism (VTE) treatment in patients with acute leukemia (AL) are not well understood and the optimal treatment strategy is unclear. METHODS: We conducted a systematic review of the literature aiming to identify observational studies and randomized trials describing treatment of VTE in the setting of AL including, acute myeloid leukemia (AML), acute promyelocytic leukemia (APL), and acute lymphoblastic leukemia (ALL). Due to the heterogeneity of findings, no meta-analysis was attempted. RESULTS: A total of 13 observational studies (11 cohorts and 2 case-control) totaling 5359 participants were included. The number of patients with VTE among the total population was 304 (5.7%; 95% CI 5.1-6.3). In patients with VTE, 221 patients received treatment with anticoagulation using either of low-molecular-weight heparin, unfractionated heparin, and/or vitamin K antagonists. Most studies adjusted the anticoagulant dose based on platelet count. The reported recurrence rate ranged from 0 to 29% among different studies and varied according to the duration of anticoagulant treatment and follow up. Bleeding events were not uniformly reported but the total number was low among anti-coagulated patients. CONCLUSION: There is a significant lack of data in this area with a high degree of heterogeneity in the choice of anticoagulant, dose adjustments for thrombocytopenia, and duration of anticoagulation. Further studies are required to develop guidelines and suggestions for treatment of VTE in AL.

Prevention of venous thromboembolism in pregnant patients with a history of venous thromboembolic disease: A retrospective cohort study.

BACKGROUND: Optimal prophylactic strategies in pregnant women with a history of venous thromboembolism (VTE) are unknown. PATIENTS AND METHODS: We conducted a retrospective cohort study of consecutive pregnant patients with a previous VTE history. Patients were followed until 6 weeks postpartum. Patients with a previous unprovoked event (including antepartum VTE) received antenatal prophylaxis, mostly with low dose low molecular weight heparin (LMWH). All patients received prophylaxis for six weeks after delivery. RESULTS: We included a total of 199 pregnancies in 142 women. Of these, 147 pregnancies occurred in women with unprovoked or estrogen-related VTE history and 52 pregnancies in women with provoked VTE. There were 8 recurrences in 199 pregnancies (4%; 95%CI: 2.05-7.73), of which 5 were antepartum recurrences (2.5%; 95%CI 1.08-5.75) and 3 were postpartum (1.5%; 95% CI 0.51-4.34). In the unprovoked VTE group there were 7 recurrences (4.7%; 95%CI: 2.32-9.50), whereas in the provoked VTE group there was 1 (1.9%; 95%CI: 0.34-10.12). There was one major bleeding event in a patient not receiving LMWH secondary to placental abruption. CONCLUSION: This study suggests that the use of prophylactic doses of LMWH during pregnancy and puerperium, as described in this study, results in low occurrence of ante- and postpartum VTE recurrences in patients with previous VTE. Further studies are required to confirm this observation.

Post-transplant consolidation plus lenalidomide maintenance vs lenalidomide maintenance alone in multiple myeloma: A systematic review.

BACKGROUND: In newly diagnosed multiple myeloma (NDMM), autologous stem cell transplantation (ASCT) remains the standard approach for transplant-eligible patients. To control the inevitable relapse, post-transplant consolidation/maintenance strategies are commonly used. However, the benefit of post-transplant consolidation is still uncertain METHOD: We conducted a systematic review of phase II/III studies to compare the efficacy of post-ASCT consolidation plus lenalidomide maintenance (CON+LEN) vs lenalidomide maintenance alone (LEN alone) in NDMM. A meta-analysis using fixed and random effects models was performed. RESULTS: Fourteen studies were included with 2275 participants with NDMM treated with ASCT and lenalidomide maintenance. Two groups were identified: CON+LEN group (n = 1102) and LEN alone group (n = 1173). There was no statistically significant difference in the complete response rate between the two groups [RR = 1.1; 95% CI: 0.83-1.44; P = .490]. Interestingly, we found that very good partial response or better rate is around 1.5-fold significantly higher in the CON+LEN group compared to LEN alone group [RR: 1.46; 95% CI: 1.25-1.70; P < .0001]. However, there was no significant difference between the two groups regarding PFS [RR: 1.0; 95% CI: 0.92-1.08, P = .929] and OS [RR: 0.9; 95% CI: 0.92-1.01; P = .148] at 3-4 years follow-up. The risk of secondary primary malignancy (SPM) was also similar between the two groups (RR: 1.2; 95% CI: 0.84-1.92; P = .2). Data on adverse events were limited. CONCLUSION: Our data suggest that, in NDMM patients treated with upfront ASCT, post-transplant consolidation may improve depth of response, but does not add to OS or PFS, compared to lenalidomide maintenance alone. However, data in this context are still immature.

Retinal vein thrombosis: The Internist's role in the etiologic and therapeutic management.

Retinal vein occlusion is a common and important cause of vision loss. In general, knowledge about this condition is scant within an internist's practice but the condition is relevant because of its association with other chronic ailments. A diagnosis of RVO should prompt the investigation of conditions needing chronic management in these patients. In this review we summarize the clinical presentation of RVO, its classification, associated risk factors, and treatment focused in the internist's scope of practice.

Eculizumab in the management of paroxysmal nocturnal hemoglobinuria: patient selection and special considerations.

Paroxysmal nocturnal hemoglobinuria (PNH) is a nonmalignant clonal disorder resulting from somatic mutation in the PIG-A gene leading to a deficiency of the membrane-anchoring molecule glycosylphosphatidylinositol. The lack of expression of two glycosylphosphatidylinositol-anchored proteins involved in the regulation of the complement system renders PNH erythrocytes susceptible to complement-mediated lysis. Clinical manifestations include thromboembolic disease, chronic kidney injury, pulmonary hypertension, smooth muscle dysfunction, and chronic hemolysis. Until recently, treatment was mainly supportive with most patients suffering from significant morbidity and shortened survival compared to age-matched controls. The development of eculizumab, a humanized monoclonal antibody directed against the terminal complement protein C5, has resulted in dramatic improvements of survival and reduction in complications. In this paper, we review some special considerations pertaining to the use of eculizumab for PNH.

Randomized double-blind safety comparison of intravenous iron dextran versus iron sucrose in an adult non-hemodialysis outpatient population: A feasibility study.

BACKGROUND: Intravenous iron therapy is a treatment option for iron deficient patients who are intolerant to oral iron or where oral iron is ineffective, but with possible adverse effects. Currently, prospective studies comparing different intravenous iron formulations are needed to determine safety and efficacy of these agents. METHODS: We conducted a prospective, double-blind, randomized controlled trial (RCT) to assess the feasibility of a trial comparing the safety of high molecular weight intravenous iron dextran, Infufer®, with intravenous iron sucrose, Venofer®, in non-hemodialysis adult outpatients. Primary outcome was the occurrence of immediate severe drug reactions. RESULTS: We enrolled 143 patients in a one-year period. Overall, 45/143 (31.5 %) patients (20 iron dextran, 25 iron sucrose) developed 48 infusion reactions (14 immediate, 28 delayed, and 3 both). The risk of an immediate reaction was similar in both groups, 9/73 (12.3 %) iron dextran versus 8/70 (11.4 %) iron sucrose, RR = 0.93 (95 % CI; 0.38 to 2.27). The risk of a delayed reaction was significantly higher in the iron sucrose group 22/70 (31.4 %) versus the iron dextran group 9/73 (12.3 %), RR = 2.55 (95 % CI; 1.26 to 5.15; p = 0.0078). CONCLUSION: In this limited feasibility study, no major differences in immediate reactions were seen, but a significantly higher number of delayed reactions were seen in the iron sucrose group. Further, under our assumptions and design a full RCT to evaluate the safety of different intravenous iron preparations is not feasible. Future studies should consider modifying the clinical outcomes, utilize multiple centers, and consider other emerging parenteral iron formulations. (ClinicalTrials.gov NCT005936197 January 3, 2008).

Thromboprophylaxis in multiple myeloma patients treated with lenalidomide - A systematic review.

BACKGROUND: Studies have consistently demonstrated the need for venous thromboembolism (VTE) prophylaxis in patients with newly diagnosed multiple myeloma (NDMM) or relapsed refractory multiple myeloma (RRMM), receiving lenalidomide-based therapy. However, the optimal approach has not yet been established. OBJECTIVE: To compare the efficacy of aspirin (ASA) and low molecular weight heparin (LMWH) prophylaxis in patients with myeloma using lenalidomide-based therapy. RESULTS: Six studies were included with 1125 adult participants with NDMM or RRMM treated with lenalidomide-based therapy with thromboprophylaxis with ASA or LMWH. Pooled data of studies of NDMM showed that the risk of VTE in patients on ASA was 1.5 per 100 patient-cycles with a total risk of VTE of 98 of 915 (10.7%) [95% CI: 8.86-12.88] compared to 3 of 211 (1.4%) [95% CI: 0.48-4.09] with LMWH in NDMM and RRMM patients. Our study demonstrated a significantly higher VTE risk for patients receiving lenalidomide plus high-dose dexamethasone (RD) on ASA prophylaxis compared to lenalidomide plus low-dose dexamethasone (Rd) [RR=2.5 (95% CI: 1.68-3.96), P<0.0001]. Furthermore, patients who received lenalidomide and dexamethasone alone had a significantly higher risk of VTE compared to those on MPR while on ASA prophylaxis (RR=6.4 [(95% CI: 4.11-9.91), P<0.0001]). CONCLUSION: The most frequent thromboprophylaxis option used for myeloma patients on lenalidomide-based therapy is ASA. However, ASA may not confer appropriate thromboprophylaxis in patients using RD, but may be a safe option with MPR. In future studies, the IMWG VTE risk stratification criteria should be validated, incorporating the thromboprophylaxis option accordingly. More studies comparing the efficacy and safety of ASA to LMWH are warranted.

Identifying venous thromboembolism and major bleeding in emergency room discharges using administrative data.

BACKGROUND: Administrative data can be used to identify venous thromboembolism (VTE) and major bleeding (MB) events. However, the validity of this data in emergency room discharge records in Canada is unknown. METHODS: We conducted a single-institution retrospective chart re-abstraction study in London, Canada. We identified all adult patients with a VTE or MB code included in the mandatory Canadian Institute for Health Information National Ambulatory Care Reporting System seen at our institution between July 2002 and March 2014. VTE was defined using the International Classification of Diseases, 10th revision (ICD-10CM) codes for deep venous thrombosis (DVT), and pulmonary embolism (PE) whereas MB was defined using codes for intracerebral hemorrhage, subarachnoid hemorrhage, subdural hemorrhage, upper, and lower gastrointestinal bleeding. A random sample of 50 patients was obtained for each condition. Two abstractors independently conducted blinded diagnostic adjudication using standard criteria. Agreement was calculated using kappa statistics. Positive predictive values were calculated for VTE, MB and each diagnosis. RESULTS: Overall, ICD-10CM codes demonstrated very good ability to identify major bleeding events (PPV 88%). Diagnostic codes performed particularly well for all intracranial and lower gastrointestinal bleeds. In contrast, ICD-10CM codes for VTE had moderate ability (PPV 49%). Diagnostic codes for PE performed better than those for DVT. CONCLUSION: Single ICD-10CM codes for venous thromboembolism have moderate predictive value for identifying DVT and PE in emergency room discharges. In contrast, codes for MB events have very good ability and it would be adequate to use them for research purposes.

Screening of patients with idiopathic venous thromboembolism for paroxysmal nocturnal hemoglobinuria clones.

Paroxysmal nocturnal hemoglobinuria (PNH) is an uncommon disorder characterized by hemolysis, thrombosis and marrow failure. Whereas venous and arterial thrombosis is a very common symptom of the disease, the frequency of PNH clones in patients with unexplained venous thromboembolism, including deep vein thrombosis and pulmonary embolism, has not been studied. We conducted a cross sectional study evaluating the presence of PNH clones in patients with prevalent venous thromboembolism using a high sensitivity flow cytometry assay for erythrocytes and neutrophils. Among the 388 patients enrolled in the study one patient had a detectable PNH clone of 0.02% in the neutrophil population (0.26%; 95% CI 0.05 to 1.45) and no detectable erythrocyte clone. We conclude that the presence of PNH clones in patients with idiopathic venous thrombosis is rare. Screening for PNH clones among VTE patients might be better reserved for patients with signs of hemolysis.