Glanzmann Thrombasthenia: A Case Report of a Rare Inherited Coagulation Disorder Presenting with Traumatic Head Injury

This case study deals with a 32-year-old Indian male patient who presented with a traumatic head injury in the hospital, experienced uncontrolled bleeding after conducting surgery, and was eventually diagnosed with Glanzmann thrombasthenia. Glanzmann thrombasthenia is a rare hereditary blood clotting disorder characterised by a lack of platelet aggregation due to the absence of platelet glycoprotein IIb/IIIa. This occurrence is generally triggered by consanguineous marriages and is apparent in approximately one in one million people. Education and raising awareness about consanguinity in communities may help to reduce challenging, unusual genetic diseases.

Management of Multiple Myeloma in Older Patients

Multiple myeloma is a condition that affects predominantly the older population. There are now various approved chemotherapy regimens as a result of advances in treatment. Choosing the optimal regimen for older patients with myeloma remains a challenge because of frailty and a lack of head-to-head comparisons between backbone regimens. The purpose of this literature review is to summarise the recent literature on frailty assessment, disease biology, and treatment efficacy in the frontline and relapsed settings to aid the decision-making process.

Current and Future Therapies for β-Thalassaemia: A Review Article

This article will review recent and forthcoming advances in the treatment of thalassaemia. Prognosis of thalassaemia has dramatically improved in the last 50 years with the development of regular and safe blood transfusions and iron chelation. Almost 20 years ago, development of oral chelators, and more recently the improvement in the knowledge and understanding of iron pathophysiology, have led to optimal iron toxicity prevention and treatment. These considerable advancements in medical therapy have transformed transfusion-dependent thalassaemia from a lethal childhood disease to a chronic disease with an open prognosis, even in those individuals over 50 years of age, and with the disease being, in some instances, curable. In the 1980s, the introduction of allogeneic haematopoietic cell transplantation provided the possibility of curing the congenital disease for the first time. More recent developments include an improved understanding of erythropoiesis, which led to the development of new erythroid-stimulating factors effective in thalassaemia, an expansion of donor pull for transplantation, and the approach of the long-term promised gene therapy in clinical practice. Moreover, ongoing trials of gene editing and agents modulating iron metabolism promise new improvements. Today, patients with thalassaemia have several weapons in their therapeutic arsenal and, hopefully, will have much more to come. As usual in medical practice, new advancements provide new challenges for the medical community, and it is the duty of this community to clearly understand the benefits and challenges of any new approach in order to provide the highest clinical benefit to patients.

Isatuximab and Belantamab Mafodotin: A Primer to an Evolving Multiple Myeloma Landscape

Multiple myeloma (MM) continues to be an incurable disease impacting mainly an ageing population. Comorbidities, disease characteristics, and drug toxicity profiles heavily influence treatment selections. Despite single agent activity of many anti-MM agents, opportunities to maintain responses most often include combination therapy with immunomodulator and/or proteasome inhibitor therapies. Monoclonal antibodies (moAb) have become an additional backbone to both newly diagnosed and relapsed or refractory transplant eligible and ineligible patients. Tolerability of these agents offers an additional benefit particularly to an ageing population. Two newly approved moAb targeting CD38 and B-cell maturation antigen have been added to the anti-MM arsenal. Isatuximab, a chimeric anti-CD38 moAb, is the second U.S. Food and Drug Administration (FDA)-approved CD38 targeted therapy offering unique mechanisms of action owing to differences in epitope binding and favourable side effect profiles. Belantamab mafodotin, a B-cell maturation antigen drug-antibody conjugate, is a first-in-class humanised moAb containing a distinct microtubule-disrupting agent: monomethyl auristatin-F. Its distinctive anti-MM activity includes antibody-dependent cellular cytotoxicity and phagocytosis, as well as direct cytotoxicity caused by internalisation of monomethyl auristatin-F. This review focusses primarily on the mechanisms of action, resistance patterns, and clinical utility of two recently FDA approved agents; isatuximab in combination with pomalidomide and dexamethasone for relapsed or refractory MM exposed to at least two or more lines of therapy, and belantamab mafodotin monotherapy in relapsed or refractory MM exposed to four or more lines of therapy.

Pneumoperitoneum, Pneumothorax, and Pneumoretroperitoneum Post Colonoscopy: A Case report and Review of Literature

Colonic perforation post colonoscopy is rarely seen; however, when coupled with massive pneumoperitoneum in haemodynamically stable patients, a real dilemma for surgeons is created. The decision between watchful waiting versus surgical intervention is the real challenge and while most surgeons will urge for surgical intervention, conservative management on the other hand can be safely applied in selected haemodynamically stable patients.

Is Allogeneic Stem Cell Transplantation a Good Option for Paroxysmal Nocturnal Haemoglobinuria?

Paroxysmal nocturnal haemoglobinuria (PNH) is a rare, nonmalignant, haematopoietic clonal disorder that manifests with haemolytic anaemia, thrombosis, and peripheral blood cytopenias. The diagnosis is based on laboratory findings of intravascular haemolysis and flow cytometry. Clinical findings in PNH include haemolytic anaemia, thrombosis in atypical sites, or nonspecific symptoms attributable to the consequences of haemolysis. Thrombosis is the leading cause of death in PNH. Terminal complement pathway inhibition with eculizumab controls most of the symptoms of haemolysis and the life-threatening complications of PNH. However, there is still no consensus about haematopoietic stem cell transplantation (HSCT) in the management of PNH; it is the only potentially curative therapy for PNH. There are limited data and few case series about both the long-term outcomes of HSCT for PNH and the impacts of conditioning regimens on PNH clones. The authors have reviewed the findings of these studies which report on HSCT for the treatment of PNH.

Expanding the Role of CAR-T Cell Therapy to Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disorder resulting from autoantibodies produced by B-cell derived plasma cells. Clinical presentation ranges from mild skin rash to multiorgan failure. Regardless of the clinical presentation or severity of the disease, patients with SLE often require life-long treatment. Current treatment recommendations for SLE include hydroxychloroquine, glucocorticoids, immunomodulatory agents, cyclophosphamide, and biologic agents. Despite availability of these agents, the condition of some patients with SLE progressively worsens. With limited treatment options, new and novel therapeutic approaches are needed. Given the active role of B cells in the pathophysiology of SLE, they present an attractive target for therapies evolving in the oncology field. Amongst these, immune effector cell therapies, including chimeric antigen receptor (CAR)-T cell therapy, have proven beneficial in targeting B cells. The eradication of B cells, along with the potential for T cell persistence, has resulted in prolonged remission or stable disease. This review provides an overview of the pathophysiology of SLE; current treatment options, including monoclonal antibodies targeting cluster of differentiation-20 (CD20), CD22, and B cell-activating factor (BAFF); and explores why and how immune effector cell therapies may prove a promising therapeutic option for this patient population, particularly for individuals with refractory disease. Clinical implications from currently approved U.S. Food and Drug Administration (FDA) agents for haematologic malignancies are discussed and provide insight into considerations for applying this therapy to the patient population with SLE in the context of clinical trials.

Pregnancy-Related Thromboembolismin Sickle Cell Disease

Haematological disorders are predominant in the tropical and subtropical countries where major problems of sickle-cell disease (SCD) and thalassaemias are often recorded. However, reports of these conditions have increased in the Western hemisphere more recently. Genetic counselling, early detection of the disease condition, and determining an appropriate treatment regimen remains the solution. Most molecular types of SCD have been determined and the pathological impact of individual types along with the degree of severity is known to clinical investigators and physicians. There is, however, a significant need for a proper counselling system for the clinical diagnosis in most countries. Lack of funding, trained personnel, relevant physicians, instruments, and laboratories are the challenges to overcome. Pregnancy-associated SCD and thromboembolism require special mention due to their mortality rate, complexity of treatment, and care necessities. This review considers some of the most important aspects of pregnancy-associated SCD and thromboembolism, shedding light on the present understanding of the disease condition, pathology, clinical issues, the association with venous thromboembolism, recent treatment measures, and clinical and social management of pregnant women and fetuses for patients with SCD. Integrated social and clinical care along with extensive timely medical and clinical counselling for patients can improve the present situation which is growing in different countries. To save future generations and pregnant mothers from the haematological disorders that could be either prevented or treated, essential genetic screening or counselling should be made a priority by governments. In addition, social education and campaigns related to the disease condition can help to improve the situation.