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Shouki Bazarbashi,1 Heba Mohamed El Zawahry,2 Tarek Owaidah,3 Mohammad A AlBader,4 Ashraf Warsi,5– 7 Mahmoud Marashi,8,9 Emad Dawoud,10 Hassan Jaafar,11 Sherif M Sholkamy,12 Fady Haddad,13 Alexander T Cohen14 1Section of Medical Oncology, Oncology Center, King Faisal Specialist Hospital and Research Center, Alfaisal University, Riyadh, Saudi Arabia; 2Department of Medical Oncology, The National Cancer Institute, Cairo University, Cairo, Egypt; 3Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Center, Alfaisal University, Riyadh, Saudi Arabia; 4Hematology Unit, Al Sabah Hospital, South Surra, Kuwait; 5Department of Adult Hematology, Princess Noorah Oncology Center, King Abdulaziz Medical City, Ministry of National Guard Health Affairs–Western Region, Jeddah, Saudi Arabia; 6College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs–Western Region, Jeddah, Saudi Arabia; 7King Abdullah International Medical Research Center, Ministry of National Guard Health Affairs-Western Region, Jeddah, Saudi Arabia; 8Hematology Department, Dubai Hospital, Dubai, United Arab Emirates; 9Department of Hematology, Mediclinic City Hospital, Dubai, United Arab Emirates; 10Department of Oncology, Tawam Hospital, Al Ain, United Arab Emirates; 11Department of Oncology, Sheikh Khalifa Specialty Hospital, Ras Al-Khaimah, United Arab Emirates; 12Department of Vascular Surgery, Ain Shams University, Cairo, Egypt; 13Vascular and Endovascular Surgery, American University of Beirut Medical Center, Beirut, Lebanon; 14Department of Haematological Medicine, Guy’s and St Thomas’ Hospitals NHS Foundation Trust, King’s College London, London, UKCorrespondence: Shouki Bazarbashi, Section of Medical Oncology, Oncology Center, King Faisal Specialist Hospital and Research Center, Alfaisal University, 1 Alzahrawi Street, Riyadh, 11211, Saudi Arabia, Tel +966 505443546, Email bazarbashi@gmail.comAbstract: 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.Plain Language Summary: 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, drug–drug 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.Keywords: anticoagulation, apixaban, cancer, vitamin K antagonist, low-molecular-weight heparin

Ahmad A Alharbi,1,2 Abdullah A Alharbi,2,3 Dhafer Salem Bashen,2 Tarek Owaidah4 1Pathology Department, College of Medicine, Majmaah University, Al Majmaah 11952, Riyadh, Kingdom of Saudi Arabia; 2Laboratory Department, Dr. Sulaiman Al-Habib Hospital in Al Takhassusi, Riyadh, Kingdom of Saudi Arabia; 3Pathology Department, College of Medicine, Imam Muhammad Ibn Saud Islamic University, Riyadh, Kingdom of Saudi Arabia; 4Hematology and Transfusion Medicine Department, Alfaisal University, Riyadh, Kingdom of Saudi ArabiaCorrespondence: Tarek Owaidah, Consultant Hematology and Transfusion Medicine, Alfaisal University, P.O.Box 5092, Riyadh, 11533, Kingdom of Saudi Arabia, Tel +966 50 531 2925, Email towaidah@gmail.comBackground: Iron supplementation is administered orally or intravenously to treat iron-deficiency anemia (IDA). Ferric Carboxymaltose (FCM) “Ferinject®” is an intravenous (IV) iron preparation that has emerged as a safe therapeutic option for treating IDA in the past decade.Aim: This study aimed to evaluate safety and efficacy of carboxymaltose in a cohort of patients with IDA not responding to oral therapy.Methods: This 12-month retrospective study included 106 patients with IDA, with-or without bariatric surgery, who received (single or multiple doses) of Carboxymaltose 500mg/10mL. Data points included patients’ demographics, baseline data for Hb, platelet, ferritin, and MCV pre–and at 1, 2, and 3 months following different doses of IV-Carboxymaltose. Changes in Hb, MCV, platelets, and ferritin levels were recorded in response to Carboxymaltose to assess the optimal dose, risk of hyperferritinemia, and hypophosphatemia.Results: At three months (95 days) follow-up, the median change pre-and post-therapy in hemoglobin was from 9.5 to 11.9g/dL (p < 0.01), MCV 73.6– 80.5fL (p < 0.01), and ferritin 5.3– 93.8ng/mL. A significant difference was observed between platelet count of patients who underwent bariatric surgery and those who did not. An optimal ferritin response (> 30ng/mL) was observed in 87.8% of patients who received first dose, and none of the full three doses showed no response. 37% of patients who received two doses developed hyperferritinemia. Serum phosphate levels were assessed in 28 cases, and hypophosphatemia was observed in 25% of these patients.Conclusion: Carboxymaltose is a reliable option for IDA. IV-FCM therapy helps achieve significant improvement in hemoglobin concentration and MCV from the first dose carrying a low reversible risk of hyperferritinemia following multiple doses. An interesting finding of this study is the discovery of a population of IDA patients requiring periodic assessment for iron reinfusion to sustain normal levels, mostly post-bariatric surgery. Changes in serum phosphate levels reported to occur consecutively with FCM treatment should be further studied.Keywords: iron deficiency, anemia, ferrous carboxymaltose, hypophosphatemia

Esra’a Abudouleh,1 Ahmad Alhamshari,2 Ahmed A Al-Qahtani,3,4 Amelita Aguilos,5 Tarek Owaidah5 1Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, Saudi Arabia; 2College of Medicine, Alfaisal University, Riyadh, Saudi Arabia; 3Department of Infection and Immunity, Research Centre, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia; 4Department of Microbiology and Immunology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia; 5Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi ArabiaCorrespondence: Tarek Owaidah, Tel +966 114647272, Email towaidah@kfshrc.edu.saAbstract: Thrombosis and coagulopathy have been found to be the most prevalent complications in patients with COVID-19. Thromboprophylaxis to prevent thromboembolic events is recommended for hospitalized COVID-19 patients. Heparin-induced thrombocytopenia (HIT) is a known complication of heparin use. This study aimed to determine the incidence of HIT among admitted patients with confirmed COVID-19 by PCR. In this study, two different HIT assays, rapid immunoassay (STic Expert HIT, Stago) and H-PF4 specific enzyme-linked immunosorbent assay (Asserachrom® HPIA – IgG), were performed. Of 200 patients with confirmed COVID-19, we identified 49 patients who met the possibility of HIT (low platelet count and high D-Dimer level). Only five (10.2%) had a positive HIT rapid test. However, none of the tested samples tested positive by ELISA. Thrombosis was reported in two of five (40%) patients. Further extensive studies are required to determine the prevalence and clinical significance of a positive HIT test among patients with COVID-19.Keywords: COVID-19, thrombosis, coagulopathy

Mahasen Saleh,1 Amani Alkofide,1 Anfal Alshammari,1 Khawar Siddiqui,1 Tarek Owaidah2,3 1Department of Pediatric Hematology Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, 11533, Kingdom of Saudi Arabia; 2Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, 11211, Kingdom of Saudi Arabia; 3Department of Pathology, Alfaisal University, Riyadh, 11533, Kingdom of Saudi ArabiaCorrespondence: Tarek Owaidah Email towaidah@kfshrc.edu.saBackground: COVID-19 wreaked havoc on the healthcare system, with more than 36 million cases reported globally. Although the pediatric population makes up a lesser proportion of total COVID-19 patients than adults, the clinical status, age and comorbidities warrant identifying possible prognostic factors associated with disease severity in this group. The current study aimed to explore the incidence of thrombosis, overall outcome, and different hematological and coagulation markers in children with COVID-19.Methods: This is a single-center prospective study of 43 patients (age < 14 years) with confirmed COVID-19 diagnosis recruited from April to August 2020. Data for clinical presentation were collected and analyzed. The samples were tested for different hematological and coagulation markers.Results: Twenty-nine (67.4%) were symptomatic at presentation, with fever being the most common symptom (n = 23, 53.5%), followed by respiratory (n = 5, 11.6%) and gastrointestinal symptoms (n = 3, 7%). Co-morbid conditions were recorded in 26 (60.5%) patients, with malignancy being the commonest (n = 9, 20.9%). In this cohort of patients with age < 14 years, hypertension, respiratory symptoms and ABO group-A were significantly associated with pediatric intensive care unit (PICU) admission during the course of treatment. Patients with elevated FVIII and fibrinogen levels at presentation were more likely to have an extended length of hospital stay (LOS) (P–value =0.036 and 0.032 respectively). No thrombotic event was observed in our cohort. D-dimer values were higher (above 0.5 μg/mL) in 24 (55.8%) patients at admission. We found an association between high D-dimer and PICU admission and LOS.Conclusion: Although we did not observe thrombosis in our cohort, serial measurements of D-dimer and elevated FVIII bear a prognostic value in predicting the need for critical care in children with COVID-19. Further studies with larger sample size can aid in the establishment of prognostic factors for the pediatric COVID-19 population.Keywords: COVID-19, children, hematological and coagulation markers