One of the risk factors for cardiovascular disease is Diabetes. In fact, there is a 2-4 fold increase in the risk of dying from heart disease if the patient is diabetic. One of the reasons is increased production of thromboxane which is a vasoconstrictor and at the same time promotes platelet aggregation.

Acetylsalicylic acid (Aspirin).

Aspirin, or acetylsalicylic acid is a non-steroidal anti-inflammatory drug that has many effects. It is an anti-pyretic, an analgesic and, an anti-inflam-matory drug. It also acts as an anti-platelet because it irreversibly inhibits the  formation of thromboxane through the cyclooxygenase I pathway.

The American Diabetes Association and the American Heart Association have endorsed the following guidelines: “Aspirin may be used in women over 60 and men over 50 who have diabetes mellitus who have other risk factors for heart attack and stroke.”

A study by Spectre, et.al. showed that twice daily dosing of aspirin improved the laboratory outcomes in high-risk DM II patients. The laboratory parameters used were impedance aggregometry (WBA) and the IMPACT-R (CPA). 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.

One cannot discount the importance of platelet concentrates as a treatment for many bleeding disorders. Many patients with platelet dysfunctions rely on platelet transfusions. A case in point, platelet concentrates are a lifesaving measure in patients with Dengue Hemorrhagic Fever.

Platelet concentrates are ideally transfused as soon as they are collected but can be stored for up to 5 days when kept on a rotator at 20-24 degrees Celsius. It is important that platelets be kept in continuous gentle rotation to keep them suspended in plasma and prevent aggregation.

Issues with transporting and storing platelets may be a stumbling block in areas where a pheresis machine is not readily available. Platelet concentrates are expensive to obtain and its use should be optimized. One way to make sure that the platelet concentrates are still potent is through testing and monitoring its adhesion and aggregation capabilities. Studies have been done using the IMPACT-R machine as a monitoring tool. An abstract of one such study can be found here.

Impact-R may be used in platelet function studies of patients with Storage Pool Disease.

Platelet Storage Pool Disease(SPD) involves disorders with reduction in the number and contents of platelet granules. These may be a-granules, d-granules, or a combination of both. The most common of which is d-SPD, and  the rarest is ad-SPD. The Gray Platelet Syndrome is an a-SPD where there is severe reduction of the number and contents of a-granules. The defect can be

Hermansky-Pudlak syndrome.

of two modalities, one wherein the SPD is restricted to the platelets and another where it is part of systemic syndromes with defective assembly and packaging of granules. An example would be Hermansky-Pudlak syndrome where the patient has oculocutaneous albinism, bleeding disorders, and cellular storage disorders.

SPD is an autosomal recessive trait but can also be an acquired disorder.  It may be seen in patients with myeloproliferative disorders, myelodysplasia, acute leukemia, and even systemic lupus erythematosus (SLE).  Treatment is supportive, and may involve platelet transfusions.

IMPACT-R is a cone and plate analyzer that can be used for the study of platelet function, either hyper- or hypo-function. It is an important screening tool for platelet abnormalities and may be used as a monitoring tool for therapeutic response in patients being treated.