Impact-R, a cone and platelet analyzer can be used to determine the effect of increased erythrocyte and thrombocyte counts on platelet adhesion and aggregation.

In a study by Peerschke, et.al., the cone and platelet analyzer was used to determine platelet adhesion in terms of surface coverage (%SC) and platelet aggregation in terms of aggregate size (AS in um).

A blood clot on electron microscopy.

The study noted that erythrocytosis increased aggregate size and thrombocytosis increased surface coverage. The specimen used was whole blood from healthy individuals with varying RBC and platelet counts.

The study also investigated blood from individuals with myeloproliferative diseases. They noted that differences in the platelet function parameters were seen in MPD patients undergoing different therapies.

Thrombin is a powerful platelet agonist.

Impact R is a useful tool to assess platelet function in different hematologic diseases and to monitor anti-platelet therapy.  In the study by Shenkman, et.al., Impact-R was used to test agonist-induced platelet aggregation.

Some of the known platelet agonists are: ADP, epinephrine, arachidonic acid, gamma-thrombin, and collagen. In the aforementioned study, they used ADP, ristocetin, epinephrine, collagen and arachidonic acid. These agonist act through various mechanisms that affect different stages of the coagulation process.

The Impact-R agonist response test detected platelet aggregation defects in patients with storage pool disease, von Willebrand disease and epinephrine response deficiency.  It may be useful in determining response to various platelet agonists.

This is a case of a 79-year old man with severe aortic stenosis and recurrent GI bleeding. This case study by Schmid, et.al. proposes that Impact-R to determine platelet function may be more time- and cost-effective compared to electrophoretic analysis of vWF multimers.

Severe aortic stenosis with bleeding diathesis is also known as Heyde syndrome. The pathophysiology: loss of high molecular weight vWF multimers in high shear stress conditions leads to a platelet type von Willebrand disease (acquired vWD, vWD type 2B) which can explain the bleeding tendencies of a patient with severe aortic stenosis.

Chediak-Higashi syndrome can also be found in killer whales.

Chediak-Higashi syndrome (CHS) is a rare autosomal recessive mutation in the LYST gene. This results in microtubule defects in the cell that causes decreased phagocytosis. The decreased phagocytic activity of the cells in the body leads to recurrent pyogenic infections, skin pigmentation disorders and peripheral neuropathy. Manifestations include neutropenia, oculocutaneous albinism, periodontal disease, and bleeding disorders.

The bleeding disorders are heterogeneous. A study of 8 CHS patients by Al-Sheyyab, et.al. pointed out several mechanisms for the bleeding diathesis in CHS. In one patient, there is abnormal aggregation due to storage pool deficiency (SPD) of ADP and serotonin. In another patient, the aggregation defect resembles that of von Willebrand disease type IIb. Other defects involved the dense bodies and the alpha-granules as well as the platelet membrane.

An avenue of research in the pathophysiology of CHS is therefore opened up by these findings. What are the different platelet defects associated with CHS? What are the different mechanisms leading to an abnormality in platelet aggregation? What is the effect of ristocetin in platelet aggregation and how is this significant in CHS patients. The use of Impact-R will greatly aid the researcher in the investigation of the abovementioned issues.

The aortic valve is the valve between the left ventricle and the aorta, the main artery. It has three leaflets (tricuspid). When the left ventricle contracts, it pushes blood through the valves and into the aorta. When the left ventricle relaxes, the valves close, preventing the blood from flowing back into the left ventricle.

When the aortic opening becomes constricted or stenotic, the blood in the left ventricle cannot be pumped effectively into the aorta. Aortic stenosis (AS) is usually age-related and is caused by progressive calcification of any of the three leaflets of the valve.

Severe aortic stenosis also causes an acquired form of von Willebrand disease (vWD type 2A). This is due to breakdown of the von Willebrand factor (vWF) by the increased turbulence around the stenotic valve. The increased turbulence causing high shear stress conditions predisposes the vWF to cleavage by an enzyme, ADAMTS-13. This enzyme is the 13^th member of the class of enzymes known as a disintegrin and metalloproteinase with a thrombospondin type 1 motif also known as von Willebrand factor-cleaving protease (vWFCP).

This acquired form of vWD causes bleeding in the AS patient. Whether the bleeding is due to platelet adhesion or to platelet aggregation has not been determined. This is the subject of the study done by Panzer, et.al. using the IMPACT-R machine. The study concludes that reduced levels of large vWF multimers associated with severe AS leads to impairment of both adhesion and aggregation of platelets. An abstract of the study can be found here.

Statins are a class of drugs that lower blood cholesterol by inhibiting the enzyme HMG-CoA reductase. This enzyme, found in the liver, plays an important role in the production of cholesterol. It reduces HMG-CoA to mevalonate, and this conversion is the rate-limiting step in cholesterol biosynthesis.

HMG-CoA reductase pathway and drugs that inhibit the various steps (in red).

Statins act by competitive inhibition of HMG-CoA reductase since the statins are molecularly similar to HMG-CoA. Statins are used to lower cholesterol levels in patients who have tried diet and lifestyle modifications but still have high levels of cholesterol.

Medical use of statins is to decrease mortality in patients with preexisting cardiovascular disease and those who are high-risk for developing heart disease. Researchers propose four mechanisms for reduced cardiovascular events in patients taking statins:

1. Improve endothelial function
2. Modulate inflammatory responses
3. Maintain plaque stability (in atheromas)
4. Prevent thrombus formation

It is the 4th mechanism that is the subject of a study by Matetzky, et.al., which examined the effects of statins on platelet adhesion and aggregation. This study utilized the IMPACT-R to determine aggregate size and surface coverage of platelets taken from hypercholesterolemic and STEMI (ST-elevation myocardial infarction) patients treated with statins as compared to patients not treated with statins. An abstract of the study can be found here.