Posts Tagged ‘Bernard-Soulier Syndrome’

Ristocetin and Impact-R

Tuesday, January 3rd, 2012

Impact-R determines the degree of platelet adhesion and platelet aggregation under near physiologic conditions. Platelet adhesion is expressed as %SC or the percentage of the surface covered by platelet aggregates. Platelet aggregation is expressed as AS µm2 or the average size of the aggregates.

Ristocetin.

Sometimes, a platelet agonist is needed to assay platelet function in cases where there is defective adhesion and aggregation. One of these agonists is Ristocetin. Ristocetin is an antibiotic previously used to treat staphylococcal infections. Use was discontinued because of its lethal side-effects, thrombocytopenia and platelet agglutination. Because of these same side-effects, ristocetin is now used to diagnose certain hematologic conditions such as von Willebrand disease and Bernard-Soulier syndrome.

Ristocetin causes von Willebrand factor to bind the platelet receptor GpIb so that when ristocetin is added to whole blood, it agglutinates. The mechanism for such activity is yet unexplained but there are several hypotheses including one in which the binding of ristocetin to the platelet changes its surface charge. Ristocetin will show hypoagglutination in von Willebrand disease because of a deficiency in von Willebrand factor and in Bernard-Soulier syndrome because of a deficiency in GpIb receptor proteins in the platelet cell membrane.

Tests that use ristocetin include: Ristocetin Cofactor Activity and Ristocetin Induced Platelet Aggregation.

Platelet Membrane Disorders and Impact-R

Wednesday, December 14th, 2011

Inherited platelet disorders are rare conditions that are not usually encountered in clinical practice. However, the study of the pathophysiology has led to a better understanding of platelet biochemistry and physiology. They may be subdivided into the following:

  1. Platelet Membrane Disorders
  2. Platelet Granule Disorders
  3. Macrothrombocytopenias
  4. Platelet Signaling Disorders

The Platelet Membrane Disorders:

Glanzmann’s Thrombasthenia is a rare disorder where platelets can carry out biochemical reactions but are unable to form aggregates. This is an autosomal recessive trait where platelets have absent or dysfunctional GpIIb/IIIa complexes.

Smooth inactivated platelet (blue) with spiky activated platelets (light blue). ©2000 Dennis Kunkel, Ph.D.

In a normal platelet, there are about 50,000 of these complexes in the membrane. When platelets are activated, the complex binds fibrinogen, which in turn bind to GpIIb/IIIa complexes on other platelets, resulting in multicellular aggregates. Platelets are normal in size, shape and number. Patients with Glanzmann’s Thrombasthenia have mucosal bleeding throughout life and may even have severe bleeding episodes requiring platelet transfusions.

Bernard-Soulier Syndrome is another rare autosomal recessive disorder caused by mutations of the GpIb/IX/V complex. This complex is the main receptor for von Willebrand’s factor, which anchors platelets to exposed subendothelium in cases of endothelial injury and under high shear stress. The platelets are abnormally large and the count is low. Patients present with muco-cutaneous bleeding and prolonged bleeding time. They may require platelet transfusions and sometimes respond favourably to Desmopressin.

Pseudo- or Platelet type von Willebrand Disease is an autosomal dominant disorder arising from mutations of the GpIba polypeptide that make the platelet hypersensitive to vWF. Mucosal bleeding and borderline thrombocytopenia are noted. Pseudo-vWD resembles Type IIB vWD. An accurate diagnosis is necessary since treatment differs, Pseudo-vWD requiring platelet transfusions while Type IIB vWD requires vWF transfusion.

ADP receptor Deficiency is an autosomal recessive disorder involving the ADP receptor P2Y12. ADP released from damaged tissues and activated platelets plays a role in platelet aggregation through the mediation of receptors P2Y1 and P2Y12.   P2Y1 initiates platelet response to ADP while P2Y12 forms and sustains large aggregates. Patients, therefore, have mild bleeding but are susceptible to posttraumatic and post-surgical blood loss.

Collagen receptor deficiency involves two receptors, an integrin protein, GpIa/IIa, and a non-integrin protein, GpVI. This deficiency is still under intense study.

Platelet function studies that show how platelets behave in vitro can be very helpful in diagnosis of these conditions. One of these is studying the platelet aggregates formed when blood is exposed to polystyrene in flow conditions. The IMPACT-R machine is one laboratory equipment that uses the cone and plate principal.

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