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 apheresis concentrates are an invaluable blood product in the treatment of many disorders involving platelet deficiency. Congenital diseases such as Glanzmann’s thrombasthenia, Platelet type von Willebrand disease, and May-Heggelin anomaly, as well as acquired diseases such as Dengue Hemorrhagic Fever rely on platelet transfusions.

A previous article focused on the testing of platelet concentrates as they are stored in the laboratory facility. A study by Horvath, et.al., however, tested the patient’s blood for platelet function after a platelet transfusion has been done. In many cases, the effect of a platelet transfusion is quantified as an increase in the platelet count and not the platelet function.

The use of Impact-R as a diagnostic and monitoring tool for platelet function is feasible as was concluded by Horvath, et.al.

What is a screening test? It is a device used to detect disease or a precursor of a disease in persons who do not have signs and symptoms. The decision to screen should be based on a careful history and assessment of risk factors.

Children with a family history of bleeding disorders may well benefit from a

Alexei Nikolaevich, heir to the Russian throne, had Hemophilia B.

screening test. The child’s future health and quality of life will depend on the diagnosis of a serious medical condition ahead of the time when signs and symptoms manifest. Children with a family history of congenital platelet function defects, clotting factor deficiencies, and defects in primary or secondary aggregation are among those that will put a screening test to good use.

A study by Revel-Vilk, et.al. evaluated the use of the Impact-R as a one such screening test. They concluded that the Impact-R is highly effective in excluding a bleeding disorder in patients with normal result. However, in case of abnormal Impact-R results, further testing is necessary to diagnose the condition.

Impact-R CPA test can be a useful screening test for von Willebrand Disease.

Von Willebrand Disease or vWD is the most common hereditary bleeding disorder. It is caused by a deficiency in the von Willebrand Factor (vWF).  VWF has two main functions in the coagulation cascade: 1) it is the major adhesion molecule that anchors the platelets to the exposed subendothelium, and 2) it is the binding protein for Factor VIII (FVIII). The clinical manifestations of vWD is due to its effect on platelet function.

Patients with vWD present mostly with mucosal bleeding and sometimes with post-operative bleeding.  Signs and symptoms include: bruising in uncommon areas of the body, prolonged epistaxis, heavy menstrual bleeding or menorrhagia, prolonged bleeding at dental extraction sites, or during tonsillectomies.

VWD has 3 major types (Type 1, 2, and 3) with Type 2 having 4 subtypes (Type 2A, 2B, 2M, and 2N). The most common is Type 1. The following table compares the Activated Partial Thromboplastin Time (aPTT), vWF antigen, vWF activity, and FVIII activity of the different types.

Von Willebrand factor replacement is the definitive therapy for vWD especially as prophylaxis for major procedures to reduce the risk of post-operative bleeding. For minor procedures and for mild Type 1 vWD treatment of choice is 1-deamino-8-D-arginine vasopressin (DDAVP or desmopressin) which causes the release of vWF and FVIII from endothelial stores. It can be given intravenously or by an intranasal spray.

Diagnosis is done by careful history and physical exam with a combination of several laboratory tests such as aPTT, ristocetin cofactor assay, collagen binding activity multimer assays. A useful screening test to determine decreased platelet function is the IMPACT-R Cone and Platelet Analyzer (CPA) which tests platelet adhesion and aggregation in anti-coagulated whole blood under arterial flow conditions. This test is qualitative compared to the merely quantitative platelet count.