Philippe Gaucher, A French doctor first described a condition in a 32-year old woman with an enlarged spleen in 1882. This condition would soon be known as Gaucher’s disease and its biochemical nature elucidated in 1965.

Gaucher’s disease (GD) is an autosomal recessive disorder in chromosome 1

Acid beta-glucosidase.

affecting the enzyme acid beta-glucosidase (a.k.a. lysosomal glucocerebrosidase, glucosylceramidase, D-glucosyl-N-acylsphingosine glucohydrolase). This enzyme catalyses the breakdown of glucosylceramide, a component of the cell membranes of WBC and RBC. When a macrophage phagocytoses the WBC and RBC that are due for destruction, glucosylceramide accumulates in the macrophage and cannot be eliminated.  Glucosylceramide can also accumulate in the brain  due to the rapid turnover of complex lipids during brain development and myelin sheath formation.

There are three types of GD, types I, II and III, of which type I is the most common and the least debilitating form. Unlike the other two, type I is non-neuropathic. Symptoms and signs are noted early in life or in early adulthood and includes hepatosplenomegaly, frequent infections, anemia, leukopenia and thrombocytopenia, osteoporosis and arthralgias, yellowish-brown skin pigmentation, and frequent ecchymoses and mucosal bleeding. The bleeding symptoms are sometimes noted to be disproportionate to the level of thrombocytopenia.

A research done by Spectre, et.al. proposes to clarify why the degree of mucosal bleeding does not coincide with the platelet count. His team noted that it is a defect in platelet adhesion that may be a potential cause for the bleeding. The study included patients with type I GD (with a platelet count of more than or equal to 130,000 per liter and a hematocrit of more than or equal to 30%) and healthy controls. They noted that type I GD patients had significantly lower platelet adhesion (as determined by IMPACT-R) that was not improved even with enzyme replacement therapy but was improved after splenectomy. Many of these patients also had mucosal bleeding. An abstract of the study can be found here.

What is FMD?

Brachial artery scanning to measure FMD.

Flow-Mediated Dilatation is the increase in calibre of a blood vessel in response to increased blood flow. This was first described by Schretzenmayr. FMD is endothelium dependent, wherein the endothelium acts as a mechanotransducer that senses changes in shear stress and then determines the release of dilatators. Several dilator factors have been proposed to be involved in FMD: prostaglandins , ATP or an endothelium-derived hyperpolarizing factor, and nitric oxide (NO). An increased release of NO in response to increases in shear stress causes dilatation of underlying smooth muscle of conduit arteries.

Why is FMD significant?

A decreased FMD reflects endothelial dysfunction and may predict coronary artery disease in susceptible patients. The brachial artery FMD can be measured by ultrasound scan and acts as surrogate for the coronary vasculature which can only be assessed by more invasive methods.

How is FMD related to platelet reactivity?

Another effect of NO released by the endothelium under increased shear stress is decrease of platelet reactivity. Does it follow, therefore, that if decreased FMD determines endothelial dysfunction and decreased NO release, it also determines an increased platelet reactivity?

A study by Shechter, et.al. explores the association between platelet reactivity and brachial artery FMD in controls (without established cardiovascular disease) and in patients with acute myocardial infarction. Platelet reactivity was measured by conventional aggregometry and by the IMPACT-R machine. The study concludes that FMD is inversely correlated to platelet reactivity in both controls and AMI patients. An abstract of the said study can be found here.