Prevalence and Regional Distribution of Beta-Hemoglobin Variants in Saudi Arabia: Insights from the National Premarital Screening Program".

BACKGROUND: Hemoglobinopathies are among the most prevalent inherited disorders globally, with carrier prevalence varying significantly across regions. In Saudi Arabia, high rates of consanguineous marriages amplify the risk of these disorders. AIM: This study aims to assess the burden of hemoglobinopathies by evaluating the prevalence and regional distribution of beta-hemoglobin variants, including rare variants, among couples participating in the national premarital screening program. METHODS: Data were collected from the premarital genetic screening program and entered into the SEHA platform, covering the 13 administrative regions of Saudi Arabia. Blood samples underwent various screening tests for infectious and genetic diseases. Hemoglobin electrophoresis samples were analyzed using capillary electrophoresis, High-Performance Liquid Chromatography (HPLC), or a combination of both methods. RESULTS: From 2011 to 2018, 1,871,184 individuals were included in the study, with 49.8% male and 50.2% female. The average age was 30.2 years. Hemoglobin S (HbS) was identified in 88,431 individuals (4.7% of the tested population and 78.5% of abnormal screening results), primarily as a sickle cell trait. ß-thalassemia was the second most common disorder, identified in 22,420 individuals (1.2% of the population and 19.9% of hemoglobin disorders). HbC and HbD were each detected in 0.04% of cases, while HbO-Arab was identified in 0.007% and HbG in 0.006%. Hemoglobin E and hemoglobin Lepore were found to be extremely rare. CONCLUSION: The study demonstrates regional variation in the prevalence of hemoglobin genetic variants in Saudi Arabia. To effectively mitigate this risk, it is imperative to strengthen public education and awareness, particularly focusing on genetic screening and counseling.

Multiple Myeloma: A Personal Account of My Journey With the Disease and Response to Teclistamab.

Multiple myeloma (MM) remains an incurable hematologic cancer leading to damage to the bone marrow that causes destructive bone lesions in addition to many other effects. I am a patient with MM who has undergone treatment to date since the diagnosis of this disease in December 2019. This paper reviews the treatments and observations made throughout this period. The salient results of such treatments are discussed in chronological order. During this period, my MM relapsed and then I was introduced to teclistamab treatment. The outcome of teclistamab treatment is quite promising, and I anticipate a longer life at a maintenance dose of this drug with a better quality of life. When writing this article, I am still receiving the teclistamab treatment cycles that maintain a constant normal level of my kappa-free light chain (FLC) and kappa/lambda ratio, with no significant side effects.

Consensus-Based Expert Recommendations on the Management of Hemophilia A in the Gulf Region.

BACKGROUND: Hemophilia A presents a significant health challenge in the Gulf region, where it has an especially high prevalence. There are several unmet needs associated with the management of hemophilia A in the region. The aim of this manuscript was to contextualize unmet management needs, provide recommendations to optimize care, and specify requirements for the establishment of gene therapy centers in the region. SUMMARY: An expert panel was assembled comprising ten clinical hematologists from Kuwait, Oman, Saudi Arabia, and the UAE. The Delphi methodology was used to obtain a consensus on statements relating to several aspects of hemophilia A. A consensus was reached for all statements by means of an online, anonymized voting system. The consensus statements pertain to screening and diagnosis, treatment approaches, and requirements for the implementation of gene therapy. KEY MESSAGES: There are significant challenges that hinder the optimal management of hemophilia A in the Gulf region. The consensus statements presented provide specific recommendations to improve diagnostic and treatment approaches, promote multidisciplinary care, and optimize regional data generation and reporting. These statements also delineate the requirements for the establishment of gene therapy centers for hemophilia A in the region.

Regional Prevalence of Hemoglobin C Across Saudi Arabia: An Epidemiological Survey.

INTRODUCTION: HbC is a common structural hemoglobinopathy especially in West Africa. Prevalence and regional distribution of HbC in Saudi Arabia are widely undocumented. Patients with homozygous HbC disease may have mild hemolytic anemia whereas combination with hemoglobin S (HbS) leads to a clinically severe phenotype. AIM: The current epidemiological study, considered the largest from Saudi Arabia, aimed to evaluate the regional prevalence of the HbC variant among the couples participating in the premarital screening program from 2011 to 2018. METHODS: Data from the PMSGC program were obtained for premarital screening and genetic counseling. The collected data were then entered into the SEHA platform, a centralized electronic repository for the 13 designated regions in Saudi Arabia. Hemoglobin electrophoresis samples are analyzed using either HPLC, capillary electrophoresis, or a combination of both methods to confirm the presence of abnormal hemoglobin bands. RESULTS: This study included 1,871,184 individuals from 2011 to 2018. Of those, 49.8% were males and 50.2% were females. 112,618 (6.0%) had an abnormal test. Total number of Hb C cases were 778 (0.04%). HbC trait (HbAC) was detected in 764 participants while homozygous HbC (HbCC) and combined heterozygous (HbSC) were found in 9 and 5 cases, respectively. The regions near the Red Sea have higher rates than the central and eastern regions. CONCLUSION: HbC is a rare variant in Saudi Arabia with varying regional frequencies. HbC variant is more common in Mecca and Madina regions. The geographic area of HbC distribution differs from the areas with high prevalence of HbS, which explains why HbSC disease cases are overwhelmingly rare.

Homozygous missense variant F12 (Gly506Asp) associated with severe factor XII deficiency: a case report.

BACKGROUND: Factor XII deficiency can be related to either homozygous or compound heterozygous pathogenic variants in the F12 gene. The disease is commonly known as Hageman trait and is inherited in both autosomal recessive or dominant patterns. Clinically, factor XII deficiency is not associated with bleeding but conversely has been linked to thrombotic events, recurrent pregnancy loss, and hereditary angioedema. Molecular data of F12 deficiency are scarce and have revealed varying results between cases. However, most of the reported variants are missense mutations, gross deletions, or small insertion. Factor XII deficiency has been reported in the Saudi population in several studies, either as isolated case reports or included within the studies of rare bleeding factors deficiency. However, molecular data are lacking as no case report of genetic studies related to factor XII deficiency has been published in our local population, to the best of our knowledge. CASE REPORT: Herein we describe a homozygous missense variant involving exon 12 within F12 gene (5:176,830,269 G>A; p.Gly506Asp) in a 36-year-old Saudi multiparous female referred from the surgical clinic with significantly high activated partial thromboplastin time during preoperative assessment for sleeve gastrectomy. The patient had no history of bleeding episodes during the previous deliveries nor any tooth extractions. She had single event of spontaneous abortion during the 15th week of gestation without any bleeding complication. There was no history of thrombosis or skin manifestations, and she was not taking any medicines. There was no family history of bleeding or thrombosis. Family history revealed consanguinity as the parents are first-degree cousins. Physical examination was unremarkable. Upon investigation, the prolonged activated partial thromboplastin time was fully corrected by a 1:1 mixing study with normal pool plasma while lupus anticoagulant tests were negative. Factor assays and von Willebrand factor tests are all within normal ranges except for factor XII, which was severely deficient. A homozygous missense variant involving exon 12 within F12 gene (5:176,830,269 G>A; p.Gly506Asp) was identified. CONCLUSION: F12 (5:176,830,269 G>A; p.Gly506Asp) variant is likely to be a pathogenic variant among homozygous factor XII-deficient patients. Genetic counseling and management of the patients and families should be based on clinical evaluation.

The Effects of Various Teaching Methods on Chest X-ray Interpretation Skills Among Medical Students and Interns: A Systematic Review.

Chest X-ray (CXR) is a common tool used in medical practice. Medical students and interns should acquire knowledge of CXR interpretation, as it is an essential diagnostic tool for a large spectrum of diseases. This systematic review aimed to compare the effect of different intervention techniques on the competency of medical students and interns to demonstrate the level of confidence and competence in interpreting common presentations of CXRs. The population, intervention, comparison, and outcomes (PICO) framework was used to formulate the review question. All related articles in five databases (PubMed, Web of Science, Scopus, Medline, and Embase) were retrieved and the search was completed in March 2023 with no limiters on date and time. The number of relevant studies was 469. A multi-level approach through the Rayyan platform was used for the screening and exclusion processes. Eleven articles were included in the systematic review consisting of eight randomized controlled trials, one quasi-experimental study, one cross-sectional study, and one interventional cohort. Results showed significant effects of teaching methods utilizing deductive or inductive approach, clinical history, patient care comfort survey, and SAFMEDS (Say-All-Fast-Minute-Every-Day-Shuffled). Contrarily, no significant effect was shown by flipped classroom models and mixed and blocked practice, peer-assisted learning vs. expert-assisted learning, and Chester, an artificial intelligence tool. This review identified beneficial approaches that may enhance the learning outcomes of interpreting CXRs for medical students and interns, highlighting the remarkable impact of SAFMEDS on medical students' ability to identify CXR findings as well as the availability and practicality of online and e-learning resources for students.

A Young Patient with Undiagnosed Polycythemia-Paraganglioma Syndrome: A Case Report.

BACKGROUND Erythrocytosis results from primary or secondary causes and is characterized by an increased red blood cell count. Secondary erythrocytosis is a result of an underlying cause outside the bone marrow and is often mediated by erythropoietin. Paragangliomas are rare tumors characterized by increased release of catecholamines with symptoms such as hypertension, hematuria, headache, sweating, and post-micturition syncope. Polycythemia-paraganglioma syndrome (PPS) is exceedingly rare, and reports in the literature are limited. CASE REPORT A 14-year-old female patient presented to our clinic with sweating, palpitations, and palmar erythema. The patient's history was significant for uninvestigated hypertension diagnosed at the age of 9. There was no history of smoking or illicit drug use. Blood investigations revealed an elevated hemoglobin level of 18.5 g/dL and a hematocrit of 57.5%. Whole-genome sequencing found no mutations, excluding polycythemia vera from the differential diagnosis. Computed tomography (CT) revealed 2 lesions compatible with urinary bladder paragangliomas and retroperitoneal lesions, likely representing metastatic lymphadenopathy. Whole-body gallium-68 DOTATATE PET/CT scan demonstrated significant tracer uptake within the necrotic retroperitoneal lymph nodes. However, evaluation of the bladder lesion was limited due to physiological urinary excretion of the tracer. A 24-hour urine collection demonstrated high normetanephrine levels of 24 µmol/L. These findings confirmed the diagnosis of PPS. CONCLUSIONS PPS is largely associated with HIF2A mutations. This article describes the case of a young PPS patient and highlights the importance of considering neoplasms in the differential diagnosis of hypertension in young patients. Further, it is crucial to conduct clinical investigations on young hypertensive patients to exclude underlying causes such as renal diseases, coarctation of the aorta, and neuroendocrine disorders.

Eltrombopag for tyrosine kinase inhibitors-associated thrombocytopenia in chronic myeloid leukemia.

Patients with newly diagnosed chronic-phase chronic myeloid leukemia (CP-CML) can develop cytopenias secondary to bone marrow hypoplasia after starting tyrosine kinase inhibitor (TKI) therapy. These adverse effects are usually transient, but cytopenias can persist in some patients. TKI-associated thrombocytopenia can develop in a significant proportion of CML patients and may require TKI dose reduction or dose interruptions. The thrombopoietin receptor agonist eltrombopag may improve thrombocytopenia in these patients, but the supporting literature for this approach is limited. Herein, we describe the case of a 56-year-old woman who developed persistent TKI-associated thrombocytopenia and intracranial hemorrhage. She could not tolerate full doses of imatinib and she failed to achieve a major molecular response (MMR). She responded to eltrombopag and platelet count improved, which allowed commencement and continuation of dasatinib as second-line TKI therapy, resulting in achievement of MMR. TKI-associated thrombocytopenia can cause serious bleeding and may also interfere with the management of CML by necessitating TKI dose interruption or reduction. Use of eltrombopag can help maintain adequate platelet counts and uninterrupted delivery of TKI therapy.

Current Practices and Guidelines for Perioperative Blood Management in Post-Bariatric Body Contouring Surgery: A Comprehensive Review of Literature.

With the increase in obesity prevalence, a noticeable increase in bariatric surgeries has been reported in national and international statistics. Therefore, body contouring surgeries have increased to help individuals achieve their desired body shape. Plastic surgeons need to consider potential hematologic complications that may occur in this specific group of patients before performing body contouring surgery. This review illustrates the perioperative medical, laboratory, and management strategies needed to minimize blood loss and blood transfusion requirements during body contouring. Using Google Scholar and PubMed, a comprehensive literature review was conducted to identify articles discussing post-bariatric body contouring perioperative blood management strategies, including the effects of bariatric surgery on hemostasis as well as basic hematology and coagulation. In preoperative blood management, blood investigations aid in the early detection of electrolytes, protein, and vitamin deficiencies and anemia, resulting in the early correction of nutritional deficiencies. In order to reduce postoperative complications, surgical and anesthesia techniques, as well as intraoperative pharmacological therapy, play an essential role. Postoperative blood transfusion and restrictive transfusion thresholds are tailored to the patient's needs and depend on various physiological indicators, such as heart rate, blood pressure, urine output, and laboratory findings, such as acidosis and hematocrit level. Generally, post-bariatric body contouring blood management measures are still lacking, and more research is required to develop standardized guidelines for optimizing patient safety and satisfaction.Level of Evidence III This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Response to Lisinopril in Patients with Sickle Cell Anemia and Proteinuria.

Proteinuria is a manifestation of sickle cell anemia (SCA)-related renal disease and is a risk factor of renal impairment. Angiotensin-converting enzyme (ACE) inhibitors have benefits, but their role in SCA remains undefined. This study aimed to assess the role of lisinopril, an ACE inhibitor, in reducing proteinuria in SCA patients. Thirty-five patients older than 15 years with known SCA (HbSS or HbS-ß0) and a 24-h urinary protein level of 150 mg or more participated in this study. Urine was collected over 24 h to quantify proteinuria. The patients had a mean age of 28.5 ± 6.98 years. The median 24-h urinary protein before treatment was 0.3006 g and that after treatment was 0.150 g (P = 0.01). After a median follow-up of 38 months, 24-h urinary protein decreased in 27 (77%) patients and normalized in 18 (52%) patients. Urinary protein increased in 2 (6%) patients and remained stable (no change) in 6 (17%) patients. There was no significant difference in blood pressure (BP) before and after treatment. The average dose of lisinopril was 5 mg. Twenty patients were still on lisinopril at last follow-up. The reasons for stopping lisinopril included normalization of protein, noncompliance, adverse effects, and pregnancy. Lisinopril effectively reduced proteinuria in SCA patients, without significantly reducing BP. Only a few patients developed adverse effects, including coughing, dizziness, and diarrhea. It is unclear how long lisinopril should be continued and whether it can be stopped in patients with normalized urinary protein.

Acquired isolated factor VII deficiency in a patient with myxoid pleomorphic liposarcoma, case report.

INTRODUCTION: Acquired factor VII (FVII) deficiency is a rare condition with various causes, including acquired inhibitors to FVII, liver disease, and malignancies. Myxoid pleomorphic liposarcoma is a rare and aggressive form of soft tissue sarcoma that can cause a range of clinical manifestations, including bleeding and clotting disorders. PATIENT CONCERNS AND DIAGNOSIS: We present a case report of a 21-year-old man with severe acquired FVII deficiency due to mediastinal myxoid pleomorphic liposarcoma. The patient presented with elevated International normalized ratio (INR) and a severe reduction in FVII coagulant activity, unresponsive to conventional therapy. While an acquired inhibitor to FVII was initially suspected, negative results from laboratory testing, including protein G sepharose adsorption and a Bethesda assay using Immunoglobulin G purified from patient plasma, made the diagnosis of an acquired inhibitor to FVII uncertain. INTERVENTIONS AND OUTCOME: The patient underwent surgical resection of the tumor, supported by recombinant FVII infusion, leading to the normalization of coagulation parameters. However, a relapse of the disease was detected 6 months later when he was noted to have a decline in FVII levels. CONCLUSION: This case highlights the importance of considering rare causes of bleeding and clotting disorders, particularly in unresponsive or atypical presentations. It also underscores the need for close monitoring and follow-up in patients with acquired FVII deficiency, even after successful treatment.

The Safety and Efficacy of Low-Molecular-Weight Heparin in Pregnant Women With Rheumatic Heart Disease and Valves Replacement.

BACKGROUND: In patients with rheumatic heart disease (RHD) and prosthetic valve replacement, the risk of thromboembolic complications is the highest during and immediately after pregnancy. Therapeutic anticoagulation during this period is crucial to minimize the risk of thromboembolic complications. The use of low-molecular-weight heparin (LMWH) remains an off-label indication. The type of anticoagulants used, dosing regimens, target anti-Xa levels, and frequency of anti-Xa monitoring are highly variable in the pregnant population and have been derived from pilots, observational studies, and empirical evidence. Herein, in a real-world setting, we sought to examine the efficacy and safety of variable anticoagulation options with a focus on LMWH in the management of RHD-related valvular disease in pregnant women. METHODS: This study is a retrospective study conducted at a large university-affiliated tertiary care center (King Saud University Medical City) between January 2011 and February 2020. All pregnant women with RHD who had heart valve replacements were reviewed. Patient data were extracted for demographic information, baseline characteristics, anticoagulation type, and primary outcomes. Primary endpoints were thromboembolic events, hemorrhagic complications, and fetal outcomes. RESULTS: A total of 744 pregnancies in 149 women were identified. The mean age ± SD of the women was 43.8 ± 12 years. A total of 86 women (58%) were on the LMWH regimen, 35 women (23%) were on LMWH and warfarin regimen, and 28 women (19%) were on unfractionated heparin (UFH) and warfarin regimen. Overall, thromboembolic events developed in five (0.7%) pregnancies. Of those, two were in the LMWH group, two were in the LMWH and warfarin group, and one was in the UFH and warfarin group. In addition, significant hemorrhagic complications occurred in five pregnancies. Of these, two occurred in the LMWH group, two in the LMWH and warfarin group, and one in the UFH and warfarin group. No adverse maternal and fetal outcomes were noted. CONCLUSION: This study presents the largest retrospective study of variable anticoagulation options in pregnant women with RHD and prosthetic valve replacement. LMWH is both safe and effective in preventing major thromboembolic complications compared to other forms of anticoagulation used during pregnancy.

The Clinical Conundrum of Managing Ischemic Stroke in Patients with Immune Thrombocytopenia.

Guidelines are lacking for management of acute ischemic stroke and stroke prevention in patients with immune thrombocytopenia (ITP). Our aim is to highlight the dilemma inherent in managing patients with both significant bleeding and thrombotic risk factors. In this review, we present two patients with history of ITP who presented with acute ischemic stroke and received tissue plasminogen activator (tPA) and endovascular thrombectomy (EVT), a rare management strategy in this patient population. In addition, we identified 27 case reports of ischemic stroke in patients with ITP; none of them received tPA or EVT. Furthermore, there are 92 patients with significant thrombocytopenia with no available data regarding the cause of thrombocytopenia, who were acutely treated with tPA or EVT. Conclusive evidence cannot be determined based on these limited number of cases. Future multicenter prospective cohort studies in patients with ITP are needed to provide better evidence-based treatment plans. At present, treatment of acute ischemic stroke in patients with ITP requires close collaboration between hematology and vascular neurology experts to find a balance between the benefit and risk of hemorrhagic complications.

Effect of anticoagulants on admission rates and length of hospital stay for acute venous thromboembolism: A systematic review of randomized control trials.

BACKGROUND: There is a paucity of data available on hospitalization and length of stay (LOS) for different anticoagulant therapies. We sought to compare and summarize admission rates and LOS, and describe the frequency of reporting these two outcomes in randomized control trials (RCTs) comparing different anticoagulant therapies for venous thromboembolism (VTE). METHODS: A literature search was conducted from inception to August 15, 2016 on RCTs of anticoagulant therapy for patients with VTE. Study selection, data extraction and risk of bias analysis were done by two reviewers independently. Meta-analyses were conducted for admission rates and LOS. RESULTS: A total of 4064 articles were identified. There were 74 articles of 70 studies included in the analysis. Hospitalization rates and LOS were reported in 13 (18.6%) and 12 (17.1%) of the 70 included studies, respectively. Low-molecular-weight heparin (LMWH)-treated patients were 33.0% less likely to be admitted to hospitals compared to unfractionated heparin (UFH) (RR = 0.67, 95% CI [0.58, 0.78]). The mean difference in LOS between LMWH and UFH was 2.54 days in favor of LMWH (95% CI [-4.94, -0.14]). Compared to parenteral therapy, using rivaroxaban was associated with a lower admission rate for a difference of 1.4-5.1% in VTE, 2.5% in DVT and 0.2% in PE. The LOS of patients receiving rivaroxaban was significant shorter than the LOS in parenteral therapy group for a difference of 1-5 days in VTE, 3 days in DVT and 1 day in PE. CONCLUSION: Admission rates were lower and LOS was shorter using LMWH compared to UFH and oral therapy compared to parenteral therapy for acute VTE treatment in RCTs, based on limited eligible RCTs. These crucial clinically relevant outcomes are underreported in the existing VTE clinical trials.

Short- and long-term mortality after pulmonary embolism in patients with and without cancer.

Pulmonary embolism (PE) is a major cause of mortality and morbidity. It is known that the risk of death varies by provoking factors; however, it is unknown if the risk of death persists beyond the initial diagnosis among patients with cancer-associated and non-cancer provoked patients. In this study, we aimed to investigate the effect of cancer on overall, short- and long-term mortality in a cohort of consecutive incident PE patients. Using administrative databases, we identified all incident cases of PE between 2004 and 2012 in Alberta, Canada. Cases were stratified by provoking factors (i.e. unprovoked, provoked, and cancer-associated). A multivariate Cox survival model was used to estimate the hazard ratios of short- and long-term death. We identified 8641 patients with PE, among which 42.2% were unprovoked, 37.9% were provoked and 19.9% were cancer-associated. The 1-year and 5-year survival probabilities were 60% (95% CI: 57-64%) and 39% (95% CI: 36-43%) in patients with cancer-associated PE, 93% (95% CI: 92-94%) and 80% (95% CI: 78-81%) in provoked PE, and 94% (95% CI: 93-95%) and 85% (95% CI: 83-87%) in unprovoked PE, respectively. Compared to patients with unprovoked events, both short-term and long-term survival in patients with cancer-associated PE have a higher observed risk of all-cause mortality in all age groups ( p<0.001). In contrast, patients with provoked events had a similar short- and long-term all-cause mortality. While PE has a significant mortality in all risk groups, patients with cancer have a higher risk of short-term mortality compared to patients with unprovoked PE.

Impact of Day 14 Bone Marrow Biopsy on Re-Induction Decisions and Prediction of a Complete Response in Acute Myeloid Leukemia Cases

Background: With acute myeloid leukemia (AML), there are limited data about the accuracy of day 14 bone marrow (BM) biopsies for predicting complete remission as compared to day 28 BM biopsy results. We here aimed to estimate the correlation between, and the diagnostic accuracy of, both approaches. Materials and Methods: We reviewed 84 patients with AML treated with standard induction chemotherapy to evaluate the remission rate and treatment decisions based on day 14 BM biopsy from 2000-2012. Results: Sixty five patients (77%) demonstrated remission (CR) with less than 5% blasts on their day 14 BM. Thirteen patients (16%) had residual disease (RD), and 6 (7%) were classified as indeterminate response (IR) i.e., blasts 5-20%. Two patients with RD on day 14 underwent re-induction. Out of the 17 remaining cases with RD+IR, 14 (all 6 with IR and 8 out of 11 with residual disease with no re-induction) demonstrated a morphologic complete remission (CR) on day 28 BM. The percentages for complete remissions on days 28 and 14 were significantly different [94% versus 79.3%, respectively; p=0.004, (OR= 0.143, 95% CI: 0.032-0.63)]. Day 14 BM had 82% sensitivity in predicting CR on Day 28; however, it had insufficient specificity (60%) in predicting failure of CR. Conclusions: Induction treatment response assessment based on day 14 BM does not accurately predict the response rate on day 28 and the use of day 14 BM as a sole marker of response to therapy might expose patients to unnecessary interventions.

Sex disparities in hospitalization and mortality rates for venous thromboembolism.

Venous thromboembolism (VTE) is a major health problem for both men and women. Whether sex disparities exist for outcomes after acute VTE is unknown. We sought to measure sex-specific rates of hospitalization for and mortality from acute VTE. We used a population-based administrative dataset from Alberta, Canada, covering the years 2002 to 2012. We used Poisson regression to measure the incidence rate ratio for hospitalization and Cox regression to test for sex disparities in short-term all-cause mortality after adjusting for potential confounders. Of those diagnosed with VTE, 55.9% were women. The proportion of hospitalized women for VTE was 24.4 versus 27.8% in men (p < 0.001). The risk adjusted incidence rate ratio for VTE hospitalization increased with age for both sex. While women younger than 80 years old were less likely to be hospitalized than men, sex disparities for the risk of hospitalization were not significant after age 80 (p = 0.93). The adjusted 90-day all-cause mortality rate for women was 4.0% compared to 4.9% in men (adjusted HR = 1.0, p = 0.49). Women with acute VTE were less likely than men to be hospitalized in most age groups, but sex disparities in short-term all-cause mortality were not found.

Trends in admission rates and in-hospital stay for venous thromboembolism.

BACKGROUND: Acute venous thromboembolism leads to significant morbidity and mortality. Advances in pharmacotherapy facilitate outpatient care in low-risk acute venous thromboembolism. The proportion of hospitalized acute venous thromboembolism cases and the average length of stay are not known. We sought to identify predictors of hospitalization, changes in hospitalization rates and length of stay of acute venous thromboembolism over a decade in Alberta, Canada. METHODS: Using linked administrative health databases, we identified adult patients diagnosed primarily with acute venous thromboembolism between April 2002 and March 2012. We measured trends using Poisson regression, adjusted length of stay using analysis of covariance. We identified predictors of hospitalization using multivariate logistic regression. RESULTS: 8198 out of 31,656 acute venous thromboembolism cases were hospitalized. The overall venous thromboembolism admission rates ranged between 23.7% and 27.8% with no evident temporal trend (P=0.10). The average admission rate was 51.9% for pulmonary embolism and 16.1% for deep vein thrombosis. The mean length of stay for deep vein thrombosis and pulmonary embolism remained unchanged with an adjusted mean for venous thromboembolism of 6.9±1.0days. Higher Charlson index, older age, male gender, pulmonary embolism at presentation and multiple comorbidities were associated with hospitalization. Hospitalization was associated with 30-day mortality (odds ratio:2.8, 95% CI: 2.2-3.5) whereas the length of stay was not (odds ratio:1.0, 95% CI: 0.99-1.0). CONCLUSION: Hospitalization rates and mean length of stay for acute venous thromboembolism did not change significantly between 2002 and 2012. Advances in pharmacotherapy have not yet reduced hospitalization rates or length of stay for venous thromboembolism.

Secular Trends in Incidence and Mortality of Acute Venous Thromboembolism: The AB-VTE Population-Based Study.

BACKGROUND: Venous thromboembolism is a major cause of morbidity and mortality, and comprehensive studies profiling the epidemiology and pattern of health services use are needed. In this study we provide contemporary estimates of venous thromboembolism incidence and case fatality over the past decade. METHODS: We developed a population-based venous thromboembolism dataset by linking 6 administrative health databases in Alberta, Canada from April 1, 2002 to March 31, 2012. We defined acute symptomatic cases using a validated algorithm and used Poisson regression to model annual venous thromboembolism counts. RESULTS: We identified 31,656 cases of acute symptomatic venous thromboembolism between April 1, 2002 and March 31, 2012. The age- and sex-adjusted incidence rate of venous thromboembolism was 1.38 (95% confidence interval [CI], 1.37-1.40) per 1000 person-years. For pulmonary embolism it was 0.38 (95% CI, 0.36-0.40) per 1000 person-years, and for deep vein thrombosis it was 1.0 (95% CI, 0.99-1.1) per 1000 person-years. The adjusted model showed no significant change in the incidence of venous thromboembolism during the study period. The 30-day case fatality rate of venous thromboembolism was 2.0% (95% CI, 1.89-2.21) and was almost doubled in patients with pulmonary embolism: 3.9% (95% CI, 3.50-4.33). The 1-year case fatality rate was 9.2% (95% CI, 8.88-9.52) for venous thromboembolism and 12.9% (95% CI, 12.2-13.6) for patients with pulmonary embolism. The case fatality rate increased with increasing subject age. The 1-year and 5-year survivals after first acute venous thromboembolism were similar in patients with unprovoked and provoked events. However, in patients with cancer-associated thrombosis, the 1-year and 5-year survival rate was 66% (95% CI, 64.71%-67.29%) and 46% (95% CI, 43.28%-48.72%), respectively. CONCLUSION: The incidence of acute venous thromboembolism remained unchanged over a 10-year period. However, the case fatality of venous thromboembolism is substantial.

Role of Extended Thromboprophylaxis After Abdominal and Pelvic Surgery in Cancer Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Abdominopelvic cancer surgery increases the risk of postoperative venous thromboembolism (VTE). Low-molecular-weight heparin (LMWH) thromboprophylaxis is recommended, and the role of extended thromboprophylaxis (ETP) is controversial. We performed a systematic review to determine the effect of ETP on deep vein thrombosis (DVT), pulmonary embolism (PE), major bleeding, and all-cause mortality after abdominal or pelvic cancer surgery. METHODS: A search of the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials was undertaken, and studies were included if they compared extended duration (2-6 weeks) with conventional duration of thromboprophylaxis (2 weeks or less) after cancer surgery. Pooled relative risk (RR) was estimated using a random effects model. RESULTS: Seven randomized and prospective studies were included, comprising 4807 adult patients. ETP was associated with a significantly reduced incidence of all VTEs [2.6 vs. 5.6 %; RR 0.44, 95 % confidence interval (CI) 0.28-0.70, number needed to treat (NNT) = 39] and proximal DVT (1.4 vs. 2.8 %; RR 0.46, 95 % CI 0.23-0.91, NNT = 71). There was no statistically significant difference in the incidence of symptomatic PE (0.8 vs. 1.3 %; RR 0.56, 95 % CI 0.23-1.40), major bleeding (1.8 vs. 1.0 %; RR 1.19, 95 % CI 0.47-2.97), and all-cause mortality (4.2 vs. 3.6 %; RR 0.79, 95 % CI 0.47-1.33). None of the outcomes differed if randomized trials were analyzed independently. CONCLUSIONS: ETP after abdominal or pelvic surgery for cancer significantly decreased the incidence of all VTEs and proximal DVTs, but had no impact on symptomatic PE, major bleeding, or 3-month mortality. ETP should be routinely considered in the setting of abdominal and pelvic surgery for cancer patients.