Thrombasthenia of Glanzmann a... Health Article

Definition

Thrombasthenia of Glanzmann and Naegeli is an extremely rare inherited disorder in which there is abnormal function of a component of the blood called the platelets, leading to abnormalities in blood clotting and increased bleeding.

Description

Blood clotting, or coagulation, is the process by which several factors in the blood stick together to form a physical barrier that prevents bleeding. In response to a disruption in blood flow or bleeding because of injury, several factors in the blood stick together at the site of injury, sealing off the blood vessel and stopping blood loss in a process called hemostasis. If any of the factors that contribute to the process of coagulation and hemostasis are abnormal, dangerous bleeding conditions can result.

One of the factors involved in hemostasis is called the platelet. Platelets are small disc-shaped structures that circulate in the blood stream in an inactive state. When an injury occurs, platelets become activated and stick to fibrous proteins, called fibrinogen, that are also circulating in the blood stream. Because there are multiple sites on the fibrinogen proteins for platelets to bind and vice versa, a cross-linked net or mass called a "platelet plug" is formed which seals off the injury and prevents further bleeding. Next, the platelet mass actively contracts to form an even more solid mass in a process called "clot retraction." Over time, repair cells can use this mass as a scaffolding to lay down new tissue and thereby effect a permanent repair of the injury.

Platelets attach to fibrinogen through the use of specialized sugar-proteins (glycoproteins) that are present on the platelet surface. There are two specific glycoproteins that form a complex responsible for the platelet-fibrinogen interaction: glycoprotein IIb, and glycoprotein IIIa.

The platelet disorder thrombasthenia of Glanzmann and Naegeli (TGN) results from an inherited defect in the glycoprotein IIb/IIIa complex (GP IIb/IIIa). As a result of this glycoprotein defect, platelets fail to stick to fibrinogen, leading to defective hemostasis and prolonged bleeding. TGN is sometimes subdivided into different groups: type I, in which there is no functional GP IIb/IIIa; type II, in which small amounts of working GP IIb/IIIa can be detected; and variant thrombasthenia, in which the amount of working GP IIb/IIIa may vary. Thrombasthenia of Glanzmann and Naegeli has also been referred to by other names, including: Glanzmann's thrombasthenia, diacyclothrombopathia IIb-IIIa, Glanzmann disease, and glycoprotein complex IIb/IIIa deficiency.

TGN was first described by the Swiss physician Edward Glanzmann in 1918. Glanzmann used the term, "thrombasthenia," meaning "weak platelets," because clots from patients with the disorder did not retract well. Although the disease is exceedingly rare, platelets taken from people with the disease have been very useful in the research that first discovered how normal platelets function.

Genetic profile

TGN is a genetic condition and can be inherited or passed on in a family. The disorder results from any number of different mutations that can occur in either the gene for glycoprotein IIb or the gene for glycoprotein IIIa (both located on chromosome 17, locus 17q21.32), with defects split equally between the two genes.

In the majority of cases, it appears that the genetic abnormality for the disorder is inherited as an autosomal recessive trait, meaning that two abnormal genes are needed to display the disease. A person who carries one abnormal gene does not display the disease and is called a carrier. A carrier has a 50% chance of transmitting the gene to his or her children, who must inherit one abnormal gene from each parent to display the disease. People who are carriers of the abnormal gene appear to have only half-normal amounts of working GP IIb/IIIa, which is still sufficient for normal platelet function.

There are reports of a few families in which the defect is inherited in an autosomal dominant fashion. In this pattern of inheritance, only one abnormal gene is needed to display the disease, and the chance of passing the gene to offspring is 50%.

Demographics

TGN is exceedingly rare, with less than 1,000 cases identified between 1962 and 2000. There are several groups in which the majority of cases of thrombasthenia have been discovered, including Iraqi Jews, Arabs living in Israel and Jordan, populations of south India, and French Gypsies of the Manouche tribe.