Articles & Papers

Disorders of hemostasis encompass a wide variety of conditions that interfere with the body’s ability to control bleeding. They are broadly classified into disorders of primary hemostasis, involving platelet adhesion, activation, and aggregation leading to platelet plug formation, and disorders of secondary hemostasis, involving abnormalities of the coagulation cascade and fibrin
formation.

Bleeding patterns often provide important diagnostic clues. Superficial bleeding manifestations such as epistaxis, gum bleeding, petechiae, and heavy menstrual bleeding are typically associated with platelet-related disorders. In contrast, bleeding into joints or muscles is more suggestive of coagulation factor deficiencies. However, despite important clues, a distinction between disorders
of adhesion, activation, and aggregation is unclear [2]. Although these defects have distinct pathological mechanisms, they commonly present with similar superficial bleeding symptoms, making clinical differentiation challenging. Specialized laboratory investigations are therefore essential to establish the correct diagnosis, as management strategies and long-term outcomes vary
among these disorders.

Glanzmann thrombasthenia is an inherited platelet function disorder characterized by defective platelet aggregation due to abnormalities in the glycoprotein IIb/IIIa integrin receptor evidenced by lack of in vitro coagulation to all soluble agonists [3]. Von Willebrand disease, the most prevalent inherited bleeding disorder, is inherited equally in men and women and arises from either reduced levels or impaired function of von Willebrand factor. Among its subtypes, type 2 disease is defined by qualitative defects that alter its functional activity.

Accurate differentiation between these conditions is essential, as their management strategies differ significantly. This report presents two cases that illustrate the diagnostic challenges encountered in adolescents presenting with mucocutaneous bleeding.

Glanzmann Thrombasthenia (GT) is a rare autosomal recessive bleeding disorder characterised by defective platelet aggregation due to abnormalities in the glycoprotein IIb/IIIa complex. With a lack of large real-world database studies, our study aimed to characterise the demographic, clinical and treatment profiles of GT patients using a large, national database.

Glanzmann thrombasthenia is a rare congenital platelet disorder affecting primary hemostasis, due to defective platelet aggregation and leading to mucocutaneous bleeding that can vary in severity. We report the case of a 14-month-old infant born to a first-degree consanguineous marriage, with a notable family history of unexplained severe bleeding in a maternal cousin. The patient was referred to our department for evaluation of mucocutaneous bleeding, with recurrent gingival hemorrhage and widespread ecchymoses. Initial hemostatic work-up was within normal ranges. Given the persistence of bleeding syndrome, platelet function analysis was performed, which demonstrated an aggregation defect consistent with Glanzmann thrombasthenia. This case emphasizes the diagnostic challenge of Glanzmann thrombasthenia in which routine coagulation studies are normal, and the need to maintain a high index of suspicion based on bleeding history, especially in consanguineous families. An early diagnosis is indispensable for the adequate treatment of the patient and to avoid life-threatening hemorrhagic complications.

Glanzmann thrombasthenia (GT) is a rare autosomal recessive bleeding disorder characterized by a defect in the platelet integrin αIIbβ3. While mucocutaneous bleeding is typical, gastrointestinal (GI) bleeding is not uncommon and can be a potentially severe complication.

Glanzmann Thrombasthenia (GT) results from integrin αIIbß3 defects that prevent platelet aggregation causing lifelong mucocutaneous bleeding leading to morbidity and mortality. Uncontrolled bleeding is commonly treated with platelet transfusions, antifibrinolytics, and rFVIIa. Although, there is no adequate cure for GT. Our previous preclinical studies showed proof-of-principle that hematopoietic stem cells (HSC) modified with transgenes encoding αIIbß3 provide safe and effective long-term hemostasis in GT animal models. This suggests feasibility for genetic therapy for GT patients.

Glanzmann’s thrombasthenia (GT) is an inherited platelet function disorder that may manifest with significant bleeding symptoms; in women and girls (W&Gs), heavy menstrual bleeding (HMB) is very common. GT in pregnancy is associated with an increased risk of postpartum haemorrhage (PPH).

Glanzmann thrombasthenia (GT) is a rare inherited disease characterized by mucocutaneous bleeding due to the abnormalities in quantity or quality of platelet membrane GP IIb (CD41) or GP IIIa (CD61). GP IIb and GP IIIa are encoded by the ITGA2B and ITGB3 genes, respectively. Herein, we described a 7-year-old Chinese boy of the consanguineous couple who was diagnosed with GT based on the typical clinical manifestations, absence of blood clot retraction and the reduced expression of CD41 and CD61 in platelets. A homozygous silent variant c.1431C > T (p. G477=) of the ITGB3 gene was identified by the Whole-exome sequencing and confirmed by Sanger sequencing. The variant was predicted to affect the splicing. RT-PCR and sequencing revealed that the variant caused a deletion of 95 base pairs and frameshift, and subsequently created a premature stop codon in exon 10 of ITGB3 (p. G477Afs*30). It was indicated that the variant c.1431C > T (p. G477=) of ITGB3 was the cause for Glanzmann thrombasthenia. Our findings expanded the mutation spectrum and provided the information for the genetic counseling, prenatal diagnosis and preimplantation genetic testing (PGT).

Glanzmann thrombasthenia (GT) is a genetic bleeding disorder characterised by severely reduced/absent platelet aggregation in response to multiple physiological agonists. The severity of bleeding in GT varies markedly, as does the emergency situations and complications encountered in patients. A number of emergency situations may occur in the context of GT, including spontaneous or provoked bleeding, such as surgery or childbirth. While general management principles apply in each of these settings, specific considerations are essential for the management of GT to avoid escalating minor bleeding events. These recommendations have been developed from a literature review and consensus from experts of the French Network for Inherited Platelet Disorders, the French Society of Emergency Medicine, representatives of patients’ associations, and Orphanet to aid decision making and optimise clinical care by non-GT expert health professionals who encounter emergency situations in patients with GT.

Glanzmann thrombasthenia (GT) is a rare autosomal recessive inherited platelet disorder occurring frequently in populations with high incidence of consanguineous marriages. GT is characterized by quantitative and/or qualitative defect of the platelet αIIbβ3 (GPIIb/IIIa) receptor caused by pathogenic variants of the encoding genes: ITGA2B and ITGB3. Patients present with a moderate to severe bleeding tendency with normal platelet count. Platelets show reduced/absent aggregation for all agonists except ristocetin in light transmission aggregometry and reduced/absent αIIbβ3 expression in flow cytometry (FC). In this study, we investigated a cohort of 20 Pakistani patients and 2 families collected from the National Institute of Blood Disease, Karachi and Chughtai’s Lab, Lahore. Platelet aggregation studies, FC (platelet CD41, CD61, CD42a, CD42b) and direct sequencing of the candidate genes were performed. All patients showed altered platelet aggregation, but normal agglutination after stimulation with ristocetin. Absent/reduced αIIbβ3 receptor expression was present in the platelets of 16 patients, in 4 patients expression was borderline/normal. Candidate gene sequencing identified pathogenic/likely pathogenic variants in 15 patients. Seven variants are novel. One patient with absent receptor expression remained without genetic finding. 13 (86.7%) of 15 patients stated consanguinity reflected by homozygosity finding in 14 (93.3%) patients.

Introduction: Frequent and severe bleeding events (SBE) in patients with inherited qualitative platelet disorders Bernard-Soulier Syndrome (BSS) and Glanzmann Thrombasthenia (GT) can lead to secondary iron deficiency anemia (IDA). SBE are primarily treated with platelet transfusions or recombinant activated factor VII (rFVlla) infusions. The impact of IDA on bleeding management and disease outcomes is understudied.