Glanzmann thrombasthenia (GT) is an extremely rare inherited bleeding disorder that affects platelets aggregation. This occurs because the platelet glycoprotein IIb/IIIa (GP IIb/IIIa) receptors are deficient or they are nonfunctional. Normally, the GP IIb/IIIa receptors are essential for platelets aggregation and their adherence to the endothelium. Also, these receptors are important for attracting fibrinogen from plasma to form clotting mesh with the platelets. Patients with GT are present with menorrhagia, easy bruising, purpura, epistaxis and gingival bleeding. Less common manifestations are gastrointestinal hemorrhage and hematuria. Hemarthrosis and intracranial hemorrhage are rare. On the other hand, carriers of GT appear to be asymptomatic. The onset of GT occurs at birth or early infancy as a mucocutaneous bleeding. Although this disorder is classified to be rare, its exact prevalence is still unknown; however, it is more frequent in communities where consanguineous marriages are common. Diagnosis is based on laboratory features which include normal platelet count and morphology, prolonged bleeding times, decreased or absent clot retraction, and abnormal platelet aggregation responses to physiologic stimuli.
See Saudi Arabia > El-Bostany et al., 2008
Coller et al. (1987) found that immunoblot patterns of glycoprotein IIIa could distinguish the defect present in most Iraqi-Jewish cases from that in Arab cases in Palestine.
Seligsohn et al. (1985) demonstrated that in the form of Glanzmann thrombasthenia frequent in Iraqi Jews, prenatal diagnosis is possible by means of a monoclonal antibody against GPIIb/IIIa applied to fetal blood obtained by fetoscopic venipuncture. The method would not be applicable in the rare instances of variant thrombasthenia due to a functional rather than a quantitative defect of GPIIb/IIIa.
Newman et al. (1991) demonstrated that the form of Glanzmann thrombasthenia frequent in Iraqi Jews is due to a truncated GPIIIa as a result of an 11-bp deletion within the GP3A gene, whereas the form of the disease frequent in Arabs in the Occupied Territories is due to a 13-bp deletion in the GP2B gene.
[See also: Palestine > Coller et al., 1987].
Awidi (1983) described 12 Jordanian patients in nine families. The parents were consanguineous in all instances. All patients were children with mucosal bleeding. Awidi (1983) concluded that Glanzmann disease is the second most frequent bleeding disorder in Jordan.
Accurate flow cytometric identification of types I and II Glanzmann's thrombasthenia (GT) heterozygotes was conducted by Sharp et al. (1998) by using a flow cytometric method. The study group included healthy Omani blood donors (100) as controls, five known homozygous GT patients (one with type I with absent clot retraction and four with type II with normal clot retraction), six parents of the affected homozygotes as well as seven siblings of one homozygote. The Mean Fluorescence Intensity (MFI) of normal healthy Omani subjects was found to be between 0.62 and 1.53, which showed an overlap with MFI of the six obligatory heterozygotes (0.43-0.64). This overlap was eliminated by correcting the platelet size differences on the 100 normal MFIs, which had narrowed the range to 0.80-1.21. The heterozygotes' corrected MFI did not vary significantly from the first results when each was compared with several different controls in repeat analysis and none exceeded a ratio of 0.6. This was shown by the results of one mother whose results were 0.46, 0.49, 0.52, and 0.44 over a period of two months and encompassing two batches of antibodies. By testing the seven siblings of a patient with GT, five of them had MFI results (range of 0.46-0.52) suggestive of heterozygosity.
Coller et al. (1987) used a sensitive immunoblot technique for platelet glycoprotein IIIa (GPIIIa) to analyze the platelets of four Arab patients with type I Glanzmann thrombasthenia [See: Iraq > Coller et al., 1987].
Al-Mulhim (1996) described six patients (three males and three females) from two families who were diagnosed with GT based on prolonged bleeding time, reduced clot retraction, failure of the platelet to aggregate, and a normal platelet count. All patients were found to have symptomatic petechial skin rash, which dated to early infancy. In addition, three patients had recurrent epistaxis. Two of these patients had mild neonatal bleeding; one vaginal and the other post-circumcision. One of the patients had menorrhagia at puberty. One of the male patients showed left knee hemarthrosis, a rare finding in GT. The patients were managed with platelet transfusions.
[Al-Muhlim I. Glanzman's Thrombasthenia in children with experience from the eastern province of Saudi Arabia. J Bahrain Med Soc. 1996; 8(2):90-2.]
Bashawri et al. (2005) studied the clinical presentation and laboratory findings of Glanzmann thrombasthenia (GT) retrospectively by reviewing the records of patients admitted to one hospital during 20 year period. GT was diagnosed in 30 Saudi patients (16 males and 14 females) and one Sudanese boy. Patients' age was ranging from 20 days to 71 years. First degree consanguinity was observed in 26 families (84%), while in the remaining five families, parents were related to each other in some degree. In all families, there was a positive family history in siblings and/or other family members. The patients showed epistaxis (52%), menorrhagia (35.5%), gum bleeding (32.3%), bruises (22.6%), bleeding at circumcision (13%), hemoarthrosis (13%), ecchymosis and petechial rash (16.1%), GIT bleeding (24%), hematuria (7%), delayed wound healing (3.2%), bleeding with tooth eruption (3.2%), and hemoptysis (3.2%). All patients had normal PT and APTT and all except one had a prolonged bleeding time. Normal responses to aggregation with ristocetin were observed in 18 patients, while 13 patients had reduced aggregation. Clot retraction was reduced or nil in 25 patients and normal in six patients. In four patients flow cytometric analysis of platelet membrane glycoproteins was done showing that platelet glycoproteins CD41a and CD61 were reduced in all these patients. Two sibling patients of asymptomatic first cousin parents died as a result of GT and the have another affected brother. One female patient underwent hysterectomy at the age of 25 because of intractable menorrhagia. Another male patient lost his vision in the right eye due to blunt trauma. Bashawri et al. (2005) concluded that GT might not be rare in Saudi Arabia.
[Bashawri L, Qatary A, Fawaz N, Al-Attass RA, Ahmed M. Glanzmann's thrombasthenia. Bahrain Med Bull. 2005; 27(3):]
El-Bostany et al. (2008) recruited 43 children and adolescents from Saudi Arabia and Egypt with various bleeding disorders to assess the prevalence of inherited bleeding disorders (IBD). Their ages range from 1-18 years. They also included 15 matched controls. Seven of the patients were diagnosed with platelet dysfunction. Among them two cases were diagnosed to have Glanzmann thrombasthenia. These two cases showed abnormality of aggregation with all agonists used, except for ristocetin. The authors concluded that platelets dysfunction and VWB are common in Egypt and Saudi Arabia and therefore, hematological screening should be considered routinely in children with family history of bruising or bleeding disorders.
Bashawri et al. (2005) reported a Sudanese boy with GT [See: Saudi Arabia > Bashawri et al., 2005].
Ishaqi et al. (2009) reported an 11-year-old female from the United Arab Emirates with severe Glanzmann thrombasthenia (GT) and anti platelet alloimmunization successfully treated with hematopoietic stem cell transplantation (HSCT) from her HLA-identical sibling.