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Congenital Platelet Dysfunction and von Willebrand Disease
Published in Harold R. Schumacher, William A. Rock, Sanford A. Stass, Handbook of Hematologic Pathology, 2019
Although the platelets appeared to show less than the usual amount of clumping on the peripheral blood film, this observation alone is fairly subjective, and is really not sufficient to identify the underlying problem as a platelet disorder. The normal appearance of individual platelets on the smear certainly make a gray platelet syndrome unlikely. Moreover, the normal platelet count, together with a normal mean platelet volume and normal size appearance of platelets on the peripheral blood film, are not suggestive of Bernard-Soulier disease. Glanzmann thrombasthenia deserves further diagnostic consideration, as do other disorders of platelet structure or function. While vWD remains a diagnostic possibility, the family history does not suggest that this would be of the usual autosomal dominant variety. The possibility of an autosomal-recessive type 3 vWD may essentially be excluded, since in this disorder the virtual absence of circulating vWF leads in turn to a severe deficiency of factor VIII, which would have resulted in a significant prolongation of the partial thromboplastin time.
Epistaxis
Published in John C Watkinson, Raymond W Clarke, Christopher P Aldren, Doris-Eva Bamiou, Raymond W Clarke, Richard M Irving, Haytham Kubba, Shakeel R Saeed, Paediatrics, The Ear, Skull Base, 2018
Mary-Louise Montague, Nicola E. Starritt
Nosebleeds often occur in children with thrombocytopenia either secondary to chemotherapy or a haematological disorder. It is rare, however, for haematological disorders to present with epistaxis as the primary symptom in children. Although rare, Glanzmann thrombasthenia, in which the platelet glycoprotein IIb/IIIa complex is either deficient or dysfunctional, is the commonest of the genetic platelet disorders.
Red Blood Cell and Platelet Mechanics
Published in Michel R. Labrosse, Cardiovascular Mechanics, 2018
Integrins are heterodimeric adhesion receptors formed by noncovalent association of different α and β chains and mediate platelet adhesion or platelet–platelet binding (Hynes 2002). Platelets express three β1 integrins: α5β1 (fibronectin receptor), α6β1 (laminin receptor), and α2β1 (collagen receptor). The β1 integrins were revealed to have a supportive role in platelet adhesion rather than an essential role, since GPVI was established as the major activating collagen receptor on the platelet surface (Dutting et al. 2012). On the other hand, platelets express two β3 integrins: αIIbβ3 and αVβ3 (binding to vitronectin, fibronectin, and osteopontin); the latter one is present only at very low levels. Integrin αIIbβ3 (up to 100,000 per platelet) binds several ligands, such as fibrinogen, fibrin, vWF, fibronectin, thrombospondin, and vitronectin. It plays an essential role for firm platelet adhesion on the extracellular matrix and for thrombus formation by bridging of adjacent platelets via fibrinogen or, at high shear rates, vWF (Ruggeri et al. 1999). Inherited deficiency or dysfunction of this integrin in humans results in a disorder called Glanzmann thrombasthenia, characterized by defective platelet aggregation and a severe bleeding diathesis (Nurden 2006). Mice lacking either one subunit display a similar phenotype with defective platelet aggregation and bleeding (Hodivala-Dilke et al. 1999, Tronik-Le Roux et al. 2000). To ensure firm platelet adhesion exclusively at the sites of injury, αIIbβ3 is present on the surface in a low-affinity state and shifts to a high-affinity state on cellular activation through inside-out signaling. This enables the integrin to bind tightly to its ligand, which, in turn, mediates outside-in signaling, leading to cytoskeletal rearrangement-dependent processes, such as platelet spreading (Figure 8.12a) and clot retraction (Figure 8.12b) (Ginsberg et al. 2005).
Unique case of successful surgical treatment of recurrent spinal epidural hematoma after lumbar disc surgery in a Glanzmann thrombasthenia patient
Published in British Journal of Neurosurgery, 2023
Mohammed M. Al Barbarawi, Mohammed Z. Allouh, Ziad A. Audat, Abdelwahab J. Aleshawi, Osama M. Al-Shari
Glanzmann thrombasthenia is a rare bleeding disease characterized by defective platelet aggregation.5,6 It occurs more frequently in certain ethnic populations with a high rate of consanguinity including mainly Indians and Middle Eastern populations (Saudis, Jordanians and Palestinians).5,7 Usually, GT patients are diagnosed at an early age as the hemorrhagic episodes occur during infancy and early childhood. However, it may be detected at later stages of life when the patient encounters a trauma or a surgical procedure.5 The treatment modalities include anti-fibrinolytic drugs, recombinant activated factor VII (rVIIa), hormonal contraceptives (to control excessive menstrual bleeding in females), and platelets transfusion (if bleeding is severe). However, the definite treatment is by bone marrow transplantation.5,6 In our case, the recurrent hematomas were managed by platelet apheresis and rVIIa.
Long-term treatment with thalidomide for severe recurrent hemorrhage from intestinal angiodysplasia in Glanzmann Thrombasthenia
Published in Platelets, 2021
Francesco Paciullo, Tiziana Fierro, Filippo Calcinaro, Gianfranco Zucca Giucca, Paolo Gresele, Loredana Bury
We report the case of a 66-year-old woman with Glanzmann thrombasthenia (GT) who started to show recurrent GIB, with a frequency of 2–3 episodes per month, and consequently to require repeated blood and platelet transfusions. The patient had type III GT with a homozygous p.Arg214Trp variant of ITGB3 (variant Strasbourg I), a very rare variant with only two French female patients described so far [4–6]. In our patient αIIbβ3 was expressed on the platelet surface but dysfunctional, as shown by defective PAC-1 and fibrinogen binding. Aggregation was drastically impaired in response to all stimuli except ristocetin and clot retraction was absent, in agreement with the other cases so far described (Table 1). The patient had been splenectomized at age 9 for a mistaken diagnosis of immune thrombocytopenia based only on her clinical bleeding phenotype, and later, at the age of 54 and 64, she underwent cholecystectomy for biliary gallstones and colon polypectomy with prophylactic platelet transfusions after which she started to have febrile reactions, contracted post-transfusion B-virus hepatitis, without permanent impact on her liver or coagulation parameters, and developed anti-HLA alloantibodies, still present in her blood. Throughout her life she had suffered recurrent epistaxis, menorrhagia, easy bruising and bleeding from minor wounds for which she had been treated with tranexamic acid on demand, therefore, she had a quite severe bleeding phenotype (ISTH-BAT bleeding score 23) [7].
Thrombotic complications in adult patients with severe single coagulation factor or platelet defects – an overview
Published in Expert Review of Hematology, 2019
Hanne Skaadel, Øystein Bruserud
Glanzmann thrombasthenia is an inherited autosomal recessive disorder characterized by an abnormal platelet membrane glycoprotein IIb-IIIa; this protein is crucial for platelet activation and aggregation. Patients with type 1 Glanzmann’s disease present with less than 5% of the normal glycoprotein level whereas type 2 patients have only adecrease to 10–20%; the platelet count can be slightly decreased [36]. On the other hand, Bernard–Soulier’s syndrome is a defect in the glycoprotein Ib/IX-V-complex that causes a defect binding of von Willebrand factor; these patients present with large platelets and decreased platelet counts [37]. The two diseases have a moderate to severe risk of mucocutaneous bleedings [37].