Platelets are small anucleate blood cells derived from megakaryocytes, essential for hemostasis and involved in thrombosis, inflammation, immunity, and tissue repair. Their production depends on tightly regulated processes of megakaryopoiesis and thrombopoiesis. Inherited platelet disorders (IPDs) are a heterogeneous group of rare diseases caused by germline variants affecting megakaryocyte development and maturation, platelet production, structure, or function. These include inherited thrombocytopenias, characterized by reduced platelet counts, and inherited platelet function disorders, caused by qualitative platelet defects. Depending on the underlying genetic alteration, patients may present with bleeding, syndromic manifestations, or predisposition to hematologic malignancies. Recent advances in platelet biology and molecular genetics have improved diagnosis, personalized management, and genetic counseling. In parallel, IPDs have emerged as valuable human models for understanding the molecular mechanisms regulating platelet biogenesis and function in health and disease.

von Willebrand Disease (VWD) is the most common heritable bleeding disorder worldwide and arises from quantitative or qualitative deficiencies of von Willebrand Factor (VWF). VWF is a multimeric protein essential for primary hemostasis and factor VIII stabilization. Diagnosis of VWD requires integration of bleeding history and laboratory testing. Traditional laboratory assays, such as ristocetin cofactor activity (VWF:RCo) are increasingly being replaced by newer methods with improved analytical performance, including VWF:GPIbM and VWF:GPIbR. Advances in multimer analysis, Collagen Binding, and genetic testing are further refining the approach to VWD subtype classification. This review summarizes recent diagnostic innovations.

von Willebrand disease (vWD) is the most common inherited bleeding disorder. Various subtypes of vWD exist as either quantitative deficiencies or qualitative defects of the von Willebrand factor (vWF) protein and lead to an array of bleeding manifestations. Individuals with vWD typically have increased mucocutaneous bleeding including oral mucosal bleeding, epistaxis, and heavy menstrual bleeding. Other common bleeding manifestations including petechiae, easy bruising, surgical-related bleeding, postpartum hemorrhage, and trauma-induced bleeding. In more severe subtypes gastrointestinal bleeding, hemarthrosis, and intramuscular bleeding can occur. Given the spectrum of bleeding phenotypes, management can differ greatly from one individual to the next with the majority of individuals receiving on-demand treatment while more severely affected individuals may receive long-term prophylaxis. Common on-demand therapeutics include oral, intravenous, topical, and/or intranasal antifibrinolytics, intravenous, subcutaneous and/or intranasal desmopressin, and intravenous plasma-derived and recombinant-vWF replacement therapy. Long-term prophylactic regimens include hormonal therapies and regularly scheduled infusions of plasma-derived and recombinant-vWF concentrates. Over the past 100 years the therapeutic landscape for individuals with vWD has changed significantly and continues to evolve. There are numerous studies currently underway to evaluate new treatments including several drugs administered via subcutaneous injection, and vagal nerve stimulation. Historically individuals with vWD have poorer health-related quality of life and higher healthcare resource utilization compared to the general population, emphasizing the ongoing need for improved therapeutics.

Glanzmann thrombasthenia (GT) is a rare, autosomal recessive platelet aggregation disorder caused by mutations in the ITGA2B and ITGB3 genes. These mutations result in quantitative or qualitative deficiencies in the alpha IIb beta 3 integrin complex, impairing platelet aggregation and leading to recurrent mucocutaneous bleeding. The key findings include absent or severely reduced platelet aggregation with adenosine diphosphate (ADP), epinephrine, and collagen, while aggregation with ristocetin remains normal. While hundreds of pathogenic variants have been identified, the genetic landscape of GT continues to expand with the discovery of novel mutations. GT treatment focuses on controlling bleeding. Hemopoietic stem cell transplantation (HSCT) offers a curative option for severe cases, while gene therapy is a promising future approach. Here, we report the case of a four-year-old female presenting with recurrent bilateral epistaxis and a significant family history of bleeding diathesis. Whole-exome sequencing (WES) revealed a novel homozygous missense variant in ITGA2B (c.655G>T; p.Gly219Cys). This variant, which is absent from public genomic databases, was predicted to be deleterious by multiple in-silico computational tools, supporting a diagnosis of GT. This case identifies a previously unreported pathogenic variant and underscores the critical role of genetic testing in diagnosing unexplained mucocutaneous bleeding, particularly in cases involving consanguinity.

Von Willebrand factor (VWF) is a key coagulation protein, tethering platelets to the sites of injury through binding sites for platelet glycoprotein Ibα and exposed subendothelial collagen. VWF synthesis occurs in endothelial cells and megakaryocytes, a complex process involving the VWF propeptide, dimerization and multimerization, and glycosylation. Von Willebrand disease results from defects or dysfunction in VWF and includes both quantitative and qualitative issues with the VWF protein. VWF is cleaved by ADAMTS13 and ultimately cleared from circulation. Although it is clear that VWF plays an important role in clot formation, it may also be important in a number of other areas including angiogenesis. Our knowledge of VWF has come a long way in the 100 years since the first publication by Erik von Willebrand in 1926 thanks to a large number of researchers in the VWF biology field.

Musculoskeletal pain (MSP) is a general term for pain varying by source, characterized into nociceptive (tissue pain), neuropathic (nerve pain), and nociplastic (centralized pain). It affects muscles, bones, joints, tendons, and ligaments due to multiple etiologies, including trauma, degenerative changes, or autoimmune and inflammatory disorders, presenting as either acute or chronic pain with symptoms such as sharp, dull, tingling, or burning sensations. It is a leading cause of disability globally, particularly in low and middle-income countries. We want to highlight a real-world implementation that aims to illustrate translational feasibility, and not a comparative efficacy trial on degenerative (wear and tear) conditions such as osteoarthritis and tendinous injuries. Ultrasound-guided musculoskeletal (MSK) injections offer a minimally invasive and accurate treatment option for these two conditions, especially in settings where patients can face barriers to surgical care. Traditionally, management of such cases includes analgesia, physiotherapy, and surgery. This article highlights the implementation of ultrasound-guided musculoskeletal injection procedures in a general medical and surgical clinical setting in southern Trinidad, including hyaluronic acid (HA), platelet-rich plasma (PRP), and diluted corticosteroid injections. Over the course of two years (2023-2025), a total of 115 adult patients with chronic MSP who had an unsatisfactory response to treatment with oral analgesics were treated under ultrasound guidance. The patients largely reported qualitative improvement in pain and increased functionality post-intervention. No major complications due to the procedures were observed. Through this perspective/observational experience, we do not aim to quantify the treatment effect sizes, but rather to bring to attention the practical procedural techniques, associated safety, potential workflow advantages, and practical considerations of ultrasound-guided musculoskeletal injections, thereby highlighting their use as a radiation-free, feasible, and efficient intermediate treatment option in resource-limited settings that have limited access to advanced imaging or surgical services.

Glanzmann thrombasthenia (GT) is an inherited hemorrhagic disorder characterised by impaired platelet functions, manifested clinically as spontaneous bleeding. It is usually inherited in an autosomal recessive manner. Platelet dysfunction in patients with GT is caused by quantitative and/or qualitative deficiencies in αIIbβ3, which result from mutations in the genes encoding αIIbβ3. These genetic alterations lead to platelet dysfunction characterised by impaired fibrinogen binding capacity upon agonist stimulation, defective aggregation and spreading. While classical GT typically exhibits normal platelet counts and morphology, very rare mutations in ITGA2B (encoding αIIb) and/or ITGB3 (encoding β3) cause macrothrombocytopenia or increased platelet anisotropy (heterogeneity of platelet size and morphology). This type of mutation mainly localises in the membrane-proximal region of αIIbβ3 and is inherited in an autosomal dominant manner. This particular type of disorder is called ITGA2B/ITGB3-related macrothrombocytopenia and has been considered a subset of congenital macrothrombocytopenia. Current research suggests that gain-of-function mutations in ITGA2B or ITGB3 underlie the pathogenesis of most ITGA2B/ITGB3-related macrothrombocytopenia and mechanistically distinguish it from classical GT. However, recent reports have documented non-activating ITGB3 mutations that also cause macrothrombocytopenia, presenting a profound challenge to the mechanistic understanding of ITGA2B/ITGB3-related macrothrombocytopenia. This review summarises the reported cases of gain-of-function mutations in ITGA2B and ITGB3 associated with ITGA2B/ITGB3-related macrothrombocytopenia hitherto and discusses the potential molecular pathways contributing to the unique phenotypes in ITGA2B/ITGB3-related macrothrombocytopenia.

The COVID-19 pandemic brought attention to post-viral smell distortion, or parosmia, which is defined as a qualitative dysfunction resulting from distorted odor perception in the presence of an odorous medium (1). Very often, qualitative and quantitative alterations occur simultaneously. Patients severely affected by qualitative odor disorders find that their quality of life has deteriorated (2). For quantitative loss from viruses, the role of olfactory training has been emphasized (3), along with high volume steroid nasal irrigations (4), and even injections with platelet-rich plasma (5). However, there has been no high-level evidence demonstrating an effective treatment for qualitative olfactory disorders.