Isolated neutropenia is often deemed benign in elderly patients, frequently attributed to age-related marrow changes, medications, or nutritional deficiencies. However, persistent and unexplained neutropenia may signal early clonal hematopoiesis or evolving myeloid malignancy. While acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) usually arises from multilineage cytopenia, presentation with isolated neutropenia and myeloproliferative neoplasia (MPN)-like features is exceedingly rare. This case underscores the importance of early, risk-adapted assessment in such scenarios. A 69-year-old woman presented with isolated mild neutropenia (absolute neutrophil count (ANC) 1,188/µL) and easy bruising. With no other cytopenias or symptoms, bone marrow biopsy was deferred. Six months later, she developed abdominal discomfort, anorexia, and massive splenomegaly. Laboratory tests revealed leukocytosis with left shift, anemia, thrombocytopenia, and nucleated red cells. Bone marrow biopsy showed > 40% myeloblasts, trilineage dysplasia, and mild fibrosis. JAK2 mutation and BCR-ABL were negative. Cytogenetics demonstrated i(17q) and del(20q); Fluorescence in situ hybridization (FISH) showed TP53 deletion in 81.91% of nuclei, establishing AML-MRC with high-risk features. She was started on azacitidine and venetoclax. Day 28 marrow showed minimal residual disease (blast 8%) but no metaphase growth prompting treatment continuation. She is currently on her fourth cycle with treatment-related transfusion-dependent cytopenias, prompting dose reduction. This case challenges the prevailing "watch-and-wait" paradigm in the evaluation of isolated neutropenia, particularly in older adults. It exposes the hidden risk of clinical inertia, where the absence of other overt cytopenias or symptoms may lead to missed opportunities for early diagnosis of high-risk clonal evolution. In resource-limited setting, this case underscores urgent need for heightened clinical vigilance. Likewise, it highlights the urgent need for a more risk-adapted approach to persistent isolated neutropenia and compels us to confront a critical question: how many patients are we failing to diagnose in time, and how many windows for potentially life-altering intervention are we silently allowing to close?

Vascular Ehlers-Danlos syndrome (vEDS) is a life-threatening connective tissue disorder that often remains undiagnosed before pregnancy and carries a markedly high risk of maternal mortality. We report the case of a 34-year-old pregnant woman who experienced sudden abdominal pain at 39 weeks of gestation and died shortly after delivery. Autopsy revealed an aortic rupture with histopathological findings suggestive of vEDS. Her family history included her father's sudden vascular death, and her personal history was notable for easy bruising and early-onset varicose veins. Next-generation sequencing-based postmortem genetic testing (PMGT) using formalin-fixed, paraffin-embedded liver tissue confirmed a pathogenic variant in COL3A1. This result facilitated genetic counseling for the family, allowing presymptomatic diagnosis and preventive management, including celiprolol therapy for at-risk relatives. This case underscores the value of PMGT in identifying the underlying cause of unexpected maternal death, particularly when conventional samples are unavailable.

Vitamin B12 deficiency is a common cause of normocytic or megaloblastic anemia. In 2.5% of cases, it can manifest as pseudo-thrombotic microangiopathy (pseudo-TMA), which mimics thrombotic thrombocytopenic purpura (TTP), an emergent hemolytic microangiopathy. This case report discusses a stable-appearing 45-year-old female with progressive fatigue, heavy menstrual bleeding, bleeding gums, and easy bruising. Laboratory testing demonstrated low vitamin B12 (121 pg/mL), pancytopenia, exaggeratedly elevated LDH, undetectable haptoglobin, low reticulocyte production index (RPI), and positive intrinsic factor antibody. She was diagnosed with pseudo-TMA. Unlike TTP, pseudo-TMA patients often appear clinically well and hemodynamically stable without renal or neurologic dysfunction. Other key differentiators of pseudo-TMA include progressive anemia, often with irregular red cell morphology; evidence of pancytopenia, neutropenia, and reticulocytopenia; and LDH levels exceeding 2500 units/L. While clinicians should maintain a low threshold for recognizing TTP as a hematologic emergency, they must also maintain awareness of pseudo-TMA to prevent misdiagnosis and unnecessary plasmapheresis and to optimize treatment.

Cushing's disease is a rare condition, and patients have a higher risk of thromboembolism, specifically venous events. We present a case of a middle-aged woman who underwent sleeve surgery many years ago and slowly regained weight. She had two episodes of unprovoked deep vein thrombosis (DVT), and no risk factors were identified at the time of these events. She presented 10 years later with easy bruising, myopathy, gradual weight gain, and insomnia, and was found to have ACTH-dependent pituitary Cushing's. She successfully underwent endoscopic resection of her pituitary macroadenoma. She had worsening myalgia and myopathy immediately after surgery and is now recovering from glucocorticoid withdrawal syndrome after having untreated Cushing's disease for many years. Her insomnia has resolved almost completely, she has lost 60 pounds, her hypertension has resolved completely, and now she is off medications and remains in remission after 22 months. We conclude that Cushing's disease should be viewed as a risk factor for unprovoked venous thromboembolism and screened for, especially in obese patients.

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.

Cushing's syndrome is a rare disorder caused by prolonged exposure to glucocorticoids, either from endogenous overproduction or exogenous sources, with exogenous steroid use being the most common etiology. Clinical manifestations may include moon facies, abdominal striae, easy bruising, muscle weakness, and complications such as osteoporosis and fragility fractures. Many remedies and supplements marketed for inflammatory conditions are sold online or over the counter, and some may contain hidden or undisclosed steroids that can lead to hypercortisolism. We present a case of a 52-year-old man with osteoporosis who sustained fragility fractures and became wheelchair-bound due to progressive lower extremity weakness. Evaluation demonstrated suppression of the hypothalamic-pituitary-adrenal axis, with undetectable salivary and urinary cortisol levels. Further investigation revealed long-term use of Artri King, a supplement for musculoskeletal pain that contains undisclosed glucocorticoids. This case highlights the risk of unregulated supplements causing iatrogenic Cushing's syndrome and its associated complications.

Type 3 von Willebrand disease (VWD) is the rarest and most severe form of VWD, resulting from a complete loss of function of the von Willebrand factor (VWF). This disease presents bleeding symptoms that are characteristic of primary hemostasis disorders and hemophilia-like bleeding. We present a case series of the first three patients diagnosed with type 3 VWD in Ethiopia. All three patients presented with episodes of frequent epistaxis, easy bruising, and prolonged bleeding from minor injuries. Comprehensive laboratory evaluation revealed severe anemia, markedly prolonged activated partial thromboplastin time (aPTT), complete absence of VWF, and profoundly decreased clotting factor VIII (FVIII) activity in all patients, thereby establishing the diagnosis of type 3 VWD. Patients are currently managed with frequent fresh frozen plasma, cryoprecipitate, and tranexamic acid (TXA) due to the unavailability of VWF replacement therapy in the country. For treatment response, clinical follow-up with serial aPTT monitoring was performed. Under this supportive regimen, both the frequency of mucosal bleeding episodes and the need for fresh frozen plasma (FFP) and cryoprecipitate transfusions have decreased, with transfusions required at intervals of approximately every 3-4 weeks. Thorough assessment, accurate diagnosis, and proper classification of VWD are crucial because they significantly affect patient management and treatment modalities. Type 3 VWD is often underdiagnosed and undertreated in developing countries because of the lack of available diagnostic laboratory investigations and VWF-containing concentrates.

Lipedema is a chronic adipose tissue disorder primarily affecting women, marked by abnormal, symmetrical, and disproportionate accumulation of subcutaneous fat in the lower limbs and sometimes in the arms, with hands and feet typically spared. Frequently misdiagnosed as lymphedema or obesity, lipedema presents with pain, easy bruising, bilateral nonpitting edema, and swelling that worsens throughout the day. We present two cases: Two middle-aged women reported longstanding bilateral lower limb swelling, pain, and varicose veins, without significant comorbidities. Clinical examination revealed characteristic disproportionate fat distribution and negative Stemmer's sign. Laboratory investigations and lymphoscintigraphy excluded other causes of edema. Imaging confirmed subcutaneous thickening, fat stranding, and varicosities. Both patients were advised to have conservative management including compression therapy, limb elevation, physiotherapy and dietary counseling; one patient had significant limb volume reduction. Our report underscores the importance of recognizing lipedema for early diagnosis and effective management to prevent progression and complications.

Bleeding disorder of unknown cause (BDUC) is increasingly recognized as a common diagnosis among adult patients with mild to moderate bleeding symptoms and is reflective of unremarkable hemostatic tests despite a clinically relevant bleeding tendency. While extensive clinical and basic research has been conducted on the bleeding phenotype and underlying mechanisms of BDUC, great uncertainty remains regarding the long-term risk for spontaneous bleeding and the bleeding risk after hemostatic challenges. Currently available data suggest that a substantial portion of BDUC patients continue to experience spontaneous bleeding symptoms, such as easy bruising, epistaxis, and heavy menstrual bleeding. Risk factors associated with the persistence of these symptoms include the presence of the respective symptom prior to the BDUC diagnosis and a higher baseline bleeding score. Furthermore, a large proportion of BDUC patients report bleeding complications after surgery or child delivery prior to initial investigations. Patients with prior bleeding complications after such events, patients with blood group O, and patients who did not receive hemostatic prophylaxis demonstrate an increased risk for postinterventional bleeding during follow-up. Although BDUC remains a diagnosis of exclusion, accumulating data underscore the need to recognize it as a potentially persistent clinically relevant condition. Future studies should focus on refining diagnostic algorithms, investigating underlying mechanisms, and developing predictive tools for bleeding risk to improve individualized management strategies.