The Role of Direct Oral Anticoagulants in the Treatment of Cancer-Associated Venous Thromboembolism: Review by Middle East and North African Experts.

Venous thromboembolism is a leading cause of morbidity and mortality in patients with active cancer who require anticoagulation treatment. Choice of anticoagulant is based on careful balancing of the risks and benefits of available classes of treatment: vitamin K antagonists, low-molecular-weight heparin (LMWH), and direct oral anticoagulants (DOACs). Results from randomized controlled trials have shown the consistent efficacy of DOACs versus LMWH in the treatment of cancer-associated venous thromboembolism (VTE). However, increased major gastrointestinal bleeding was observed for edoxaban and rivaroxaban, but not apixaban, compared with LMWH dalteparin. Most guidelines recommend DOACs for the treatment of cancer-associated VTE in patients without gastrointestinal or genitourinary cancer, and with considerations for renal impairment and drug-drug interactions. These updates represent a major paradigm shift for clinicians in the Middle East and North Africa. The decision to prescribe a DOAC for a patient with cancer is not always straightforward, particularly in challenging subgroups of patients with an increased risk of bleeding. In patients with gastrointestinal malignancies who are at high risk of major gastrointestinal bleeds, apixaban may be the preferred DOAC; however, caution should be exercised if patients have upper or unresected lower gastrointestinal tumors. In patients with gastrointestinal malignancies and upper or unresected lower gastrointestinal tumors, LMWH may be preferred. Vitamin K antagonists should be used only when DOACs and LMWH are unavailable or unsuitable. In this review, we discuss the overall evidence for DOACs in the treatment of cancer-associated VTE and provide treatment suggestions for challenging subgroups of patients with cancer associated VTE.

Patients with cancer are at risk of blood clots forming in their veins, which can cause illness and death. To prevent such blood clots, most patients with cancer need anticoagulant therapy. There are three types of anticoagulants available for the treatment of cancer-associated blood clots in a vein, namely, vitamin K antagonists, low-molecular-weight heparin (LMWH), and direct oral anticoagulants (DOACs). Drug trials have shown that DOACs are more effective than LMWH; however, DOACs can have a greater risk of causing major gastrointestinal bleeding. Among DOACs, edoxaban and rivaroxaban are drugs associated with higher rates of gastrointestinal bleeding. Recently updated guidelines for doctors recommend that DOACs be used as the first treatment for patients with cancer at risk of blood clot formation in a vein. For doctors in the Middle East and North Africa, this new approach differs from existing practices. Notably, choosing a treatment also depends on the type of cancer, because gastrointestinal cancers and cancers of the genitals and urinary system have an especially high risk of gastrointestinal bleeding. The choice also depends on the presence of kidney problems, drug­drug interactions, and access to the drugs. Apixaban may be the preferred DOAC in patients with gastrointestinal cancer, but this drug should be used with care in patients with upper or unresected lower gastrointestinal tumors. For patients with upper or unresected lower gastrointestinal tumors, treatment with LMWH may be preferred. Vitamin K antagonists should be used only when DOACs and LMWH are unavailable or unsuitable.

Concurrent coronary artery disease and immune thrombocytopenia: a systematic review.

Introduction: Coronary artery disease (CAD) management in the setting of immune thrombocytopenia (ITP) remains very challenging to clinicians as a reasonable balance between bleeding and thrombosis risks needs to be achieved, and the evidence guiding such management is scarce. Methods: We conducted a systematic review following the PRISMA guidelines to summarize the available literature on the management and outcomes of CAD coexisting with ITP. We searched PubMed and Embase for studies published in English exploring CAD and ITP management until 05 October 2022. Two independent reviewers screened and assessed the articles for inclusion. Patients' characteristics, CAD treatment modalities, ITP treatment, and complications were reported. Results: We identified 32 CAD cases, among which 18 cases were revascularized with percutaneous coronary intervention (PCI), 12 cases underwent coronary artery bypass graft surgery (CABG), and two cases were managed conservatively. More than 50% were men, with a mean age of 61 ± 13 years and a mean baseline platelet count of 52 ± 59 × 109/L. Irrespective of the revascularization modality, most patients were treated with either corticosteroids alone, intravenous immunoglobulins (IVIG) alone, or in combination. Among those who underwent PCI, two patients had bleeding events, and one patient died. Similarly, among those with CABG, one patient developed bleeding, and one patient died. Conclusion: We found that revascularization with either PCI or CABG with the concurrent use of corticosteroids and/or IVIG for ITP was feasible, with an existing non-negligible risk of bleeding and mortality.

Evidence-based Management of Chronic Lymphocytic Leukemia: Consensus Statements from the Gulf Region.

INTRODUCTION: Despite recent advances in diagnosis, prognostication, and treatment options, chronic lymphocytic leukemia (CLL) is still a largely incurable disease. New concepts on diagnosis, staging, treatment, and follow-up on CLL have been incorporated throughout recent years. The lack of regional consensus guidelines has led to varying practices in the management of patients with CLL in the region. AIM: This manuscript aims to reach a consensus among expert hematologists regarding the definitions, classifications, and related practices of CLL. The experts developed a set of statements utilizing their personal experience together with the current literature on CLL management. This consensus aims to provide guidance for healthcare professionals involved in the management of CLL and serves as a step in developing regional guidelines. METHODS: Eight experts responded to 50 statements regarding the diagnosis, staging, treatment, and prognosis of CLL with three potential answering alternatives ranging between agree, disagree, and abstain. This consensus adopted a modified Delphi consensus methodology. A consensus was reached when at least 75% of the agreement to the answer were reached. This manuscript presents the scientific insights of the participating attendees, panel discussions, and the supporting literature review. RESULTS: Of the 50 statements, a consensus was reached on almost all statements. Statements covered CLL-related topics, including diagnostic evaluation, staging, risk assessment, different patient profiles, prognostic evaluation, treatment decision, therapy sequences, response evaluation, complications, and CLL during the COVID-19 pandemic. DISCUSSION/CONCLUSION: In recent years, CLL management has progressed significantly with many diagnostic tests and several novel treatments becoming available. This consensus gathers decades of consolidated principles, novel research, and promising prospects for the management of this disease.

Management of humoral secondary immunodeficiency in hematological malignancies and following hematopoietic stem cell transplantation: Regional perspectives.

Secondary immunodeficiency (SID) can occur as a result of multiple factors, including hematological malignancies, hematopoietic stem cell transplantation (HSCT), immunosuppressive treatment, biologics, and anti-inflammatory drugs. SID includes disorders resulting from impairment of both cellular and humoral immunity. This review focuses on the current risk factors, implications, and challenges in managing SID patients with impaired humoral immunity, which includes quantitative (hypogammaglobulinemia) and/or functional antibody and B-cell deficiencies specifically related to hematological malignancies and post-HSCT. Increased physician awareness is needed surrounding the disease presentation and early risk factors, as SID may be caused by several etiologies. Careful clinical assessment is then required to optimize management, which encompasses close monitoring of clinical parameters, vaccination, antibiotic prophylaxis, and immunoglobulin replacement therapy (IGRT). Novel methods of IGRT administration are associated with enhanced pharmacokinetics, IgG trough level stability, no need for venous access, as well as fewer systemic adverse events and better administration flexibility compared with traditional methods. Published international guidelines supported by observations from clinical data are broadly followed; however, best practices within each country have nuances that underline the need to tailor treatment plans to the individual patient.

Applications of Artificial Intelligence in Thrombocytopenia.

Thrombocytopenia is a medical condition where blood platelet count drops very low. This drop in platelet count can be attributed to many causes including medication, sepsis, viral infections, and autoimmunity. Clinically, the presence of thrombocytopenia might be very dangerous and is associated with poor outcomes of patients due to excessive bleeding if not addressed quickly enough. Hence, early detection and evaluation of thrombocytopenia is essential for rapid and appropriate intervention for these patients. Since artificial intelligence is able to combine and evaluate many linear and nonlinear variables simultaneously, it has shown great potential in its application in the early diagnosis, assessing the prognosis and predicting the distribution of patients with thrombocytopenia. In this review, we conducted a search across four databases and identified a total of 13 original articles that looked at the use of many machine learning algorithms in the diagnosis, prognosis, and distribution of various types of thrombocytopenia. We summarized the methods and findings of each article in this review. The included studies showed that artificial intelligence can potentially enhance the clinical approaches used in the diagnosis, prognosis, and treatment of thrombocytopenia.

Thrombopoietin-receptor agonists for adult patients with immune thrombocytopenia: a narrative review and an approach for managing patients fasting intermittently.

Introduction: Thrombopoietin-receptor agonist (TPO-RAs) currently represent the state of art for treating immune thrombocytopenia. Their different molecular structures contribute to the difference in their pharmacodynamics and pharmacokinetics. This narrative review aims to provide an overview of the current TPO-RAs approved for primary immune thrombocytopenia (romiplostim, eltrombopag, avatrombopag) and the effect of intermittent fasting in adult patients receiving TPO-RAs. Areas covered: Literature was searched with no limits on date or language, using various combinations of keywords. Data on the pharmacokinetics, pharmacodynamics, efficacy, and safety of TPO-RAs and the effect of intermittent fasting were summarized. Expert opinion: Switching between TPO-RAs is a useful strategy to tackle some associated limitations. Romiplostim and avatrombopag have an advantage over eltrombopag as they do not require any dietary restrictions. In cases where romiplostim and avatrombopag are unavailable, patients should be educated on the appropriate administration, possible interactions, and dietary restrictions before initiating eltrombopag.

The Challenges in Diagnosis and Management of Acquired Thrombotic Thrombocytopenic Purpura: Consensus Report from Three Gulf Countries.

Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare hematological emergency characterized by microangiopathic hemolytic anemia, thrombocytopenia, fever, and multiorgan failure due to autoimmune-mediated deficiency in ADAMTS-13 activity. Currently, plasma exchange, with or without steroids, is the frontline option for the management of aTTP. The treatment should be started promptly once the disorder is clinically suspected. Besides, immunomodulators were studied in patients with aTTP to achieve stable remission and reduce the risk of relapse in patients with suboptimal response to plasma exchange; however, clinical trials showed equivocal results. Published data on early diagnosis, referral, and treatment patterns of aTTP patients in the member nations of the Arabian Gulf Cooperation Council (GCC) are still lacking. Therefore, the present consensus report aimed to present an overview of aTTP situation in GCC by bringing together a panel of experts from three GCC nations, to share their views on current trends and practices regarding aTTP. The experts discussed challenges including the lack of reliable data regarding the incidence of aTTP in GCC and delayed results of ADAMTS-13 activity testing. Limited patient access to tertiary centers and low level of awareness about the aTTP clinical spectrum among general practitioners are other challenges. The experts agreed that there is a need for national and regional consensus regarding the diagnosis and treatment of aTTP in the Gulf region.

Therapeutic plasma exchange followed by convalescent plasma transfusion in critical COVID-19-An exploratory study.

The pathophysiology of severe coronavirus disease 2019 (COVID-19) is primarily a host immune interplay to virus invasion. The therapeutic options have been explored either against hyperinflammation from dysregulated adaptive immunity or direct virus neutralization using antibodies from convalescent plasma (CP) of a recovered patient. The therapeutic plasma exchange (TPE) for removal of excessive inflammatory cytokines has been tried with success in COVID-19. We undertook this exploratory study to evaluate safety and efficacy of TPE followed by CP transfusion in 14 patients with critical COVID-19 requiring invasive mechanical ventilation (IMV). All patients showed improvement in symptoms and decrease of inflammatory markers especially CRP (p = 0.03). 10 patients were liberated from IMV after a median of 5.5 (3-36) days, post sequential therapy. Day 7 and Day 28 mortality was 21.4% and 28.6% respectively. The median duration ICU and hospital LOS were 12 (5-42) days and 18 (12-47) days respectively. No patient developed transfusion-associated complications, but three patients developed secondary bacterial sepsis within 14 days of therapy, and one died. This case series demonstrated the sequential use of TPE followed by CP transfusion as a therapeutic option in critical COVID-19.

Identification of microorganisms in persistent/secondary endodontic infections with respect to clinical and radiographic findings: bacterial culture and molecular detection.

BACKGROUND AND OBJECTIVES: Bacterial agents are commonly accepted as the main etiology of endodontic infections. A significant proportion of oral bacteria cannot be cultured using existing methods. Since diversity and abundance of bacterial species are different in different populations, the present study was aimed to identify effective microorganisms in persistent endodontic infections in Iranian patients based on culture and molecular biology methods using sequence analysis of 16S rDNA gene. MATERIALS AND METHODS: Thirty patients with previous failure of endodontic treatment were enrolled in the study. After isolation and disinfection of the tooth surrounding area with 3% sodium hypochlorite and 30% hydrogen peroxide, sampling from the root canals was carried out using two sterile Hedstrom files and two sterile paper points, and then the specimens were transferred to the microbiology laboratory in thioglycolate transport medium so that they undergo aerobic-anaerobic culture, PCR, and 16S rDNA gene sequencing. RESULTS: Of 30 patients (15 women and 15 men), 15 patients had radiographic lesions smaller than 5 mm and other 15 patients had radiographic lesions larger than 5 mm. The mean age of patients was 40.20 ± 13.76 years. A total of 26 patients were asymptomatic. Only four patients had clinical signs such as pain and percussion sensitivity and Tannerella forsythia was the most common bacterium found in this group of patients. 13 bacterial species were found in 11 different genus, one virus strain and one fungus strain. From 30 studied specimens, Enterococcus faecalis was the most common microorganism with prevalence rate of 63.63%. CONCLUSION: This study showed the type and prevalence of effective bacteria in secondary/persistent endodontic infections in Iranian patients. E. faecalis is the most commonly found microorganism in Iranian patients.

Peste des Petits Ruminants Virus in Vulnerable Wild Small Ruminants, Iran, 2014-2016.

In 2014-2016, >1,000 wild goats and sheep in 4 northern and central provinces of Iran died from peste des petits ruminants virus (PPRV) infection. Partial nucleoprotein sequencing of PPRV from 3 animals showed a close relationship to lineage 4 strains from China. Control measures are needed to preserve vulnerable ruminant populations.

A young patient with recurrent respiratory tract infection and anasarca.

A young man with a history of recurrent respiratory tract infections for the past 8 years presented with generalised anasarca. He was found to have advanced renal disease (stage 4) and a profound proteinuria of 82.9 g/day. Further workup revealed the presence of advanced bronchiectatic changes in the lungs. Rectal biopsy showed the characteristic pattern of amyloid deposition. A diagnosis of systemic amyloidosis secondary to bronchiectasis was made. To the best of our knowledge no other cases of bronchiectasis-associated renal amyloid disease with such marked proteinuria have been reported in the literature. Our patient had a relatively short duration between the onset of his symptoms related to underlying bronchiectasis and his clinical presentation of renal amyloidosis. He had an aggressive course of disease and unfortunately died at a very young age.

Global Risk Profile Verification in Patients with Venous Thromboembolism (GRIP VTE) in 5 Gulf countries.

BACKGROUND: The Global Risk Profile Verification in Patients with Venous Thromboembolism was the first prospective multicenter registry conducted in Arabian Gulf countries to explore the epidemiology of venous thromboembolic (VTE) disorders and to provide data on diagnosis and disease management. METHODS: Data on 242 patients with confirmed VTE were submitted between September 2003 and November 2003 from 28 contributing hospitals in the Arabian Gulf region. Differences between groups were assessed by the chi(2) test or Fisher exact test for categorical variables. The Student's t test was used for testing proportions. RESULTS: The frequency of VTE cases is deep vein thrombosis (DVT), 187 (77.27%); pulmonary embolism (PE), 35 (14.46%); and DVT with PE, 20 (8.26%). The most common symptoms of DVT and DVT/PE patients were calf pain (72%), calf swelling (63.8%), and localized tenderness (52.2%). The most common symptoms in patients with PE alone and DVT/PE were dyspnea (83.6%), thoracic pain (69.1%), and cough (40%). Risk factors for VTE were immobilization (41.3%), age >65 years (28.9%), a history of VTE (20.7%), and trauma (19%). Among surgical interventions, orthopedic procedures induced the greatest number of VTE cases, followed by general surgery and gynecological procedures. Low-molecular-weight heparins were chosen to treat 33.7% of DVT cases, whereas unfractionated heparin was used in 21.9% of cases. CONCLUSION: VTE remains a common problem in medical and surgical patients in the Arabian Gulf states. Recognition of the common risk factors is of extreme importance to implement the appropriate prophylactic strategy according to the published guidelines.

Recent advances in the diagnosis and treatment of deep vein thrombosis: a regional consensus.

Considerable progress has been made in the understanding of the risk factors for venous thromboembolism (VTE). The clinical applications of molecular techniques have allowed identification of important inherited, yet not uncommon, risk factors for VTE, such as mutations that cause Factor V Leiden and prothrombin G20210A. However, advances in our understanding have raised several questions regarding the need for, and duration of anticoagulation. At the end of the treatment period, low molecular weight heparins have become the drugs of choice and standard-of-care for VTE. In this review, cost effective diagnostic approaches for patients with suspected deep vein thrombosis, and recommended treatment options using evidence-based approaches, are described.