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. β-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.

Pure erythroid leukemia (PEL) is rare hematopoietic neoplasm characterized by uncontrolled proliferation of immature erythroid precursors—mainly abnormal proerythroblasts—comprising at least 80% of bone marrow cells. In this paper, I present a case of 48 years old patient, who presented with pancytopenia and circulating erythroblast in peripheral blood after long history of alcohol abuse. Bone marrow examination revealed hypercellular marrow which is markedly infiltrated with immature erythroid precursors. An expanded panel of immunophenotyping markers has confirmed the diagnosis of PEL. Cytogenetics analysis detected a complex karyotype with multiple chromosomal abnormalities and a novel translocation, t(8;9) (p11.2;q12), which has not been reported in acute myeloid leukemia (AML) in the past. The patient was treated with standard AML chemotherapy but he did not show an optimal response and passed away. An updated and short review about various aspects of PEL has been made with special focus on immunophenotyping and genetic studies.

Congenital Factor (F) XIII deficiency is an autosomal recessive disorder caused by genetic variations in either F13A or F13B genes leading to a bleeding diathesis with variable severity. Patients with severe FXIII deficiency usually present with umbilical cord bleeding during the neonatal period. Ecchymosis, epistaxis, and post-trauma bleeding are the most frequently reported features in FXIII deficiency. Poor wound healing and recurrent delayed bleeding episodes are typical features of factor XIII deficiency as well. Diagnosis of FXIII deficiency can be made only with a high index of clinical suspicion and sets of FXIII-directed assays, as all primary coagulation tests are typically normal. This focused review sheds light on the key points related to FXIII deficiency in the Saudi population, focusing on the clinicopathological and therapeutic aspects highlighted with an illustrative case report incidentally diagnosed during a dental procedure. The disorder is apparently underdiagnosed and underreported in the Saudi population, as only 49 cases of congenital FXIII deficiency have been reported. Moreover, no single case report of acquired FXIII deficiency has been reported in the population.

Dysregulated Wnt/β-catenin signal transduction is implicated in initiation, propagation, and poor prognosis in AML. Epigenetic inactivation is central to Wnt/β-catenin hyperactivity, and Wnt/β-catenin inhibitors are being investigated as targeted therapy. Dysregulated Wnt/β-catenin signaling has also been linked to accelerated aging. Since AML is a disease of old age (>60 yrs), we hypothesized age-related differential activity of Wnt/β-catenin signaling in AML patients. We probed Wnt/β-catenin expression in a series of AML in the elderly (>60 yrs) and compared it to a cohort of pediatric AML (2.5-fold difference (p < 0.01). A total of 36 pediatric AML (60 yrs) were identified in this cohort. Normal bone marrows (n = 10) were employed as controls. Wnt/β-catenin target genes (MYC, MYB, and RUNX1) showed upregulation, while Wnt/β-catenin inhibitors (CXXR, DKK1-4, SFRP1-4, SOST, and WIFI) were suppressed in elderly AML compared to pediatric AML and controls. Our data denote that suppressed inhibitor expression (through mutation or hypermethylation) is an additional contributing factor in Wnt/β-catenin hyperactivity in elderly AML, thus supporting Wnt/β-catenin inhibitors as potential targeted therapy.

Extramedullary hematopoiesis (EMH) is a presence of hematopoietic activity in the extramedullary sites. EMH can occur in both benign and malignant hematologic diseases. The liver and spleen are the most common sites, but may also occur infrequently at other sites. EMH often occurs in more than one site and quite rare in an isolated organ. In this study we describe an unusual case of generalized lymphadenopathy secondary to isolated extramedullary hematopoiesis as an initial manifestation of primary myelofibrosis. Computed tomography revealed generalized lymphadenopathy including mediastinal, abdominal and pelvic lymph nodes with extensive illdefined sclerotic lesions throughout the skeletal system suggestive of lymphoma/leukemia. Lymph node biopsy showed no evidence of malignancy or granuloma, however, large abnormal cells with multilobated nuclei were seen scattered in the lymph nodes. These abnormal cells were proved to be megakaryocytes. Granulocytic precursors were less obvious on the H&E section. The diagnosis was determined as EMH in the lymph node. Bone marrow (BM) examination showed hypercellular marrow for patient’s age with granulocytic and megakaryocytic proliferation with increase in BM fibrosis and reported as a myeloproliferative neoplasm, consistent with primary myelofibrosis. In summary, although EMH is not always a malignant process; it is important to stress that the patient should be investigated for underlying hematological disorders, when it is noted elsewhere.