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.

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 is 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 United Arab Emirates. 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 requirements for the establishment of gene therapy centers for hemophilia A in the region.

A 68-Year-Old Man with a Cytogenetic Diagnosis of Chronic Myeloid Leukemia and Bone Marrow Findings of Philadelphia Chromosome Translocation Between the Long Arm of Chromosomes 9 and 22, Leading to the BCR-ABL1 Fusion Gene and V617F Mutation in the JAK2 Gene.

BACKGROUND Breakpoint cluster region (BCR)-Abelson murine leukemia (ABL1) and Janus Kinase-2 (JAK2) mutations have been thought to be mutually exclusive in myeloproliferative neoplasms (MNPs), but recent data suggest that they can occur together. CASE REPORT A 68-year-old man was referred to the hematology clinic because of an elevated white blood cell count. His medical history included type II diabetes mellitus, hypertension, and retinal hemorrhage. Fluorescence in situ hybridization analysis of the bone marrow was positive for BCR-ABL1 in 66/100 cells. Conventional cytogenetics was positive for the Philadelphia chromosome in 16/20 counted cells. The percentage of BCR-ABL1 was 12%. Considering the patient's age and medical comorbidities, he was started on imatinib 400 mg once daily. Further tests showed JAK2 V617F mutation positivity and absence of acquired von Willebrand disease. He was then started on aspirin 81 mg and hydroxyurea 500 mg once daily, which was later increased to 1000 mg daily. The patient achieved a major molecular response after 6 months of treatment, with undetectable BCR-ABL1 levels. CONCLUSIONS BCR-ABL1 and JAK2 mutations can co-existence in MNPs. Physicians must suspect the presence of one of the MPNs in chronic myeloid leukemia (CML) patients with persistent or increased thrombocytosis, an atypical course of the disease, or hematological abnormalities despite evidence of response or remission of CML. Therefore, testing for JAK2 should be performed accordingly. Combining cytoreductive therapy with tyrosine kinase inhibitors (TKIs) is a therapeutic option when both mutations are present, and TKI alone is not sufficient to control peripheral blood cell counts.

The Saudi Consensus for the Management of Cancer-Associated Thromboembolism: A Modified Delphi-Based Study.

Background Cancer is a well-known risk factor of preventable thromboembolic disease. This study aims to provide guidance on the prevention and management of cancer-associated thrombosis (CT) that tailors prophylactic and therapeutic options for medical and surgical oncology patients presenting to health care settings in Saudi Arabia. Methods The present consensus was developed in concordance with the modified Delphi-based approach, which incorporates a face-to-face meeting between two voting rounds to gain experts' feedback on the proposed statements. All experts were either oncologists, hematologists, or hemato-oncologist with an active clinical and research profile in hemato-oncology. Results The experts highlighted that the comparatively high incidence of inherited thrombophilia among the Saudi population may account for a higher CT burden in the Kingdom than in other parts of the world. However, due to the lack of literature that assesses CT in Saudi Arabia, primary venous thromboembolism prophylaxis should be tailored according to a valid risk assessment of cancer patients and should be implemented in routine practice. For hospitalized medical oncology patients, the experts agreed that prophylaxis with low-molecular-weight heparin (LMWH) should be offered, regardless of the presence of acute illness. For ambulatory medical oncology patients, LMWH or direct oral anticoagulants (DOACs) prophylaxis should be offered for high-risk patients. Concerning surgical patients, they agreed that all oncology patients undergoing surgery should be offered thromboprophylaxis. In terms of secondary prophylaxis, the experts recommended continuing a prophylactic dose of anticoagulant (LMWH or DOAC), for an appropriate period depending on the cancer type and stage. Finally, they also provided a set of statements on management of CT in Saudi Arabia. Conclusion The present modified Delphi-based study combined the best available evidence and clinical experience with the current health care policies and settings in Saudi Arabia to build a consensus statement on the epidemiology, prevention, and management of CT.

Consensus recommendations on appropriate coagulation tests during emicizumab administration in Saudi Arabia.

INTRODUCTION: Emicizumab is a bispecific monoclonal antibody with the ability to bridge FIXa and FX, mimic FVIII, and restore normal hemostasis in patients with hemophilia A. Moreover, substantial evidence has shown that emicizumab-treated patients do not require monitoring, except before surgery or invasive procedures. However, introducing this novel drug to the market poses some challenges to physicians and clinical laboratories due to its interaction with conventional coagulation tests. METHODS: Given the challenges and laboratory interactions posed by this novel drug, there is an unmet clinical need to develop clear recommendations for emicizumab laboratory monitoring to highlight which laboratory tests should be used, which tests should be avoided, and when these tests should be performed. These expert recommendations are essential to prevent inappropriate testing or misleading interpretations and reduce the extra costs of unnecessary monitoring. RESULTS: A consensus meeting was conducted in December 2019, including top experts on hemophilia from Saudi Arabia, to discuss this issue. CONCLUSION: The experts agreed that, aPTT (activated Partial Thromboplastin Time)-based tests are not suitable for laboratory monitoring patients treated with emicizumab. Only FVIII chromogenic assays based on bovine FIX and FX proteins can be used to measure FVIII levels. They reviewed and recommended the type and time of testing for anti-factor VIII antibodies. Drug levels should be measured using the recommended test only when the anti-drug antibody (ADA) is clinically suspected and after excluding other causes (such as patient non-compliance).

Evaluation of a pharmacist vs. Haematologist-managed anticoagulation clinic: A retrospective cohort study.

INTRODUCTION: Warfarin is the core component in the management of various thromboembolic disorders, which requires specialized expertise to optimize outcomes. There is limited data comparing a pharmacist vs. a haematologist-managed anticoagulation clinic in our setting, and in the Middle East. We aimed to evaluate the effectiveness and safety of a pharmacist vs. a haematologist-managed anticoagulation clinic in the Ambulatory Care Center at King Abdulaziz Medical City, Jeddah, Saudi Arabia. METHODS: A retrospective cohort study was conducted from 2016 to 2018, which included adult patients who have been followed-up for at least six months and who received warfarin for an extended period. The primary outcome was the proportion of time the patients in the two arms were in the therapeutic range. The secondary outcomes were the differences in expanded time in the therapeutic range, as well as the frequency of bleeding and thromboembolic events between the two arms. RESULTS: We enrolled 104 and 124 patients in the pharmacist and haematologist arms respectively. The median time in the therapeutic range for the pharmacist arm was 71.4%, IQR (60.8-83.8) vs. 65%, IQR (43.5-79.1), in the haematologist arm (p = 0.0049). The median expanded time in the therapeutic range was 86.4%, IQR (77.5-95.3) vs. 81.21%, IQR (67.1-93.3) in the pharmacist vs. haematologist arm (p = 0.015) respectively. Major bleeding events occurred in 5.7 % vs. 3.2 %, and thromboembolic events in 5.7% vs. 4%, in the pharmacist vs. haematologist arm respectively. CONCLUSIONS: Our results demonstrated that the time in the therapeutic range was significantly higher in the pharmacist arm, with no significant difference in bleeding and thromboembolic events compared to the haematologist arm.

Splenic Infarction Induced by Dengue Hemorrhagic Fever: A Rare Presentation.

Haematological and vascular features of dengue virus infection are common and vary from tiny skin haemorrhages to significant bleeding such as epistaxis, gastrointestinal bleeding and hematuria. Spontaneous splenic rupture has also been reported as an atypical manifestation in dengue fever. We report a case of splenic infarction in a 35-year-old man who presented with fever, vomiting, diffuse abdominal pain and distention, diarrhoea, hematuria, headache, back pain, hypotension, pleural effusion and ascites. Laboratory evaluation confirmed the diagnosis of dengue hemorrhagic fever, and abdominal imaging revealed splenic infarction. He required intensive care, responded well to inotropic support and remarkably improved.

Response to imatinib therapy in adult patients with chronic myeloid leukemia in Saudi population: a single-center study.

No study has been published yet in the Arab world regarding response and outcome of imatinib in patients with chronic myeloid leukemia (CML). This study evaluated a total of 122 patients with CML treated with imatinib between 2001 and 2012. Survival, hematologic, cytogenetic and molecular responses and adverse events were assessed. The 5-year overall survival (OS), event free survival (EFS) and progression-free survival (PFS) rates were: 95.4 ± 2.3%, 81.4 ± 4.6% and 90.8 ± 3.2%, respectively. Significant differences in OS (p = 0.001), EFS (p = 0.001) and PFS (p = 0.001) were noted when patients were stratified by cytogenetic response. Survival by Sokal risk groups was not significant (p = 0.293). Complete hematologic response was achieved in 94 patients (93.1%), cytogenetic response in 84 (83.2%), major molecular response in 62 (61.4%) and complete molecular response in 34 (33.7%). This article presents the first evidence on the effectiveness of imatinib in patients with CML from Saudi Arabia and highlights similarities and differences in response patterns in published studies.