The sticky platelet syndrome

Abstract

The sticky platelets syndrome (SPS) is a procoagulant condition based on either arterial, venous, or capillary thrombi caused by hyperesponsive and hyperaggregable platelets. This is a frequent disease, which often remains clinically inapparent, until stressful events or combination with other factors increase the risk of developing SPS. The condition is due to a congenital platelet defect with autosomal dominant characteristics, leading to the increased platelet aggregability when they are challenged with epinephrine and adenosine diphosphate. Nowadays classification of this disorder is based on platelet reactivity to both ADP and epinephrine (SPS type 1), epinephrine alone (SPS type 2), and ADP alone (SPS type 3). The diagnoses of the syndrome depend on the functional aggregometer assay. This condition should be taken into account whenever a patient with thrombophilia is considered.

Keywords:

• Sticky platelets syndrome
• Thrombophilia
• Inherited coagulation disorder

In the last few decades, the knowledge of a group of conditions responsible for abnormal coagulation has become apparent. When this alteration happens in young people particularly without the usual problems that may lead to thrombosis such as smoking, high blood pressure, hyperlypidemia, venous insufficiency, diabetes mellitus, etc. we are in the setting of primary thrombophilia.¹ The definition of this condition has changed throughout the years; in the 60s thrombophilia was considered when pulmonary and leg veins were affected associated with a defect of anti-thrombin III,² this being the initially identified inherited thrombophilic condition. It was also initially thought that, in thrombophilia only veins or only arteries were involved, and in certain tissues; however, the current knowledge supports the idea that in thrombophilia, arterial, venous, or capillary trombi may present, the clinical presentation depending on the involved area.³ Thus there will be neurological, cardiac, intestinal, cutaneous, ophthalmic symptoms, etc.,⁴ as well placental thrombosis which may lead to miscarriages.^5,6

In 1988, Mammen et al.⁷ published a study of what appears to be the first large series of patients with the sticky platelet syndrome (SPS) phenotype and reinforced this information later in 1999.⁸ Patients included in this condition had coronary artery disease, transient ischemic attacks, ischemic optic neuropathy and different kinds of peripheral arterial and venous occlusions. In vitro platelet populations showed a hyperaggregable status with epinephrine and adenosine diphosphate (ADP) and they were also hyperresponsive to surface contact. Since the latter was also encountered in close family members, they thought that the syndrome was autosomic dominant and called it the SPS.⁸ At the beginning, little attention was paid to the syndrome by the medical community, but nowadays the condition has gained credibility throughout the world and is one more entity which should be added to the study of a patient with primary thrombophilia. Some patients' platelets with SPS react excessively against both epinephrine and ADP while others only against either epinephrine or ADP, these reactions are being called SPS type I, type II, or type III, respectively. Apparently there is no difference in the clinical manifestations among these three subtypes.⁹

It is necessary to state that the assay for the detection of the SPS requires a plataelet aggregometer, which is certainly not available in all standard clinical laboratories. Due to this fact and also in order to search for the pathogenesis of the syndrome it has been attempted to find a laboratory marker of the disease in lieu of the functional activity test as it is done now. In that respect there have been some trails, one involving the Gas6 protein or its polymorphism,¹⁰ and the other the glycoprotein IIIa PLA A1/aA2 polymorphism.¹¹ Both proved to be uneventful to establish a relationship between those proteins and the SPS. So, for the time being the diagnoses of the syndrome still rest in the functional aggregometer assay. Most laboratories identifying the SPS phenotype employ the same methodology; however, there is an urgent need to standardize the diagnostic methods to render comparable results.

The prevalence of the SPS phenotype is largely unknown. It was considered as an infrequent condition not worth of paying attention to, but indeed it has be said that in order to recognize its presence one has to search for it and it should be included in all the standard tests conducted to define the origin of the thrombophilia in a patient. When considering thrombophilia, either in conferences or in the literature, the idea of an abnormal coagulation FV (Factor V Leiden) almost always comes to mind¹² and this could be true for certain populations (Caucasian for example), but probably not for the rest of the world. In our country, the SPS phenotype is the second cause of thrombophilia behind the 677 methylene tetrahydro folate reductase (MTHFR) gene mutation; in others parts of the world a high prevalence of the SPS has been found as well.^13–16 The possibility about the changes in platelet responsiveness being caused by the thrombosis itself, ita est a reverse casualty possibility does not find a support in the familial distribution of the condition, being present in asymptomatic, thrombosis-free individuals.¹³ It is interesting to note that the prevalence of thrombosis in asymptomatic individuals with the SPS is unknown; we and others have shown that other thrombosis-prone conditions are needed to develop the thrombotic episode.¹⁷

With time, there has been an increase of reports that show the utility of the knowledge of the presence of SPS that leads to important therapeutic or preventive measures. There is an emerging consensus about the use of aspirin or other antiplatelet drugs in patients with the SPS phenotype in order to prevent further thrombotic episodes. Some cases of kidney grafts have ended in failure due to thrombosis related to SPS^18,19 and once the presence of SPS is recognized, proper therapeutic effort with aspirin with suitable titration of the dose have led to a successful grafting¹⁹; SPS has also being implicated in free flap failure,²⁰ and pregnancies can be successful in patients with the SPS phenotype with proper medical management, mainly aspirin or other antiplatelet drugs.²¹

In summary, it can be stated nowadays that:

a.	SPS is a real and frequent entity and its existence must be borne in mind when a cause of thrombophilic syndrome is being searched for.
b.	As most cases of thrombophilia are multifactorial,17 at this point there are no standard rules for the nature of therapy when considering several alterations. Each case has to be measured in order to create the proper therapy.
c.	Apparently there is no association among the defects.22
d.	Physicians throughout the world who care for patients with thrombophilia have to establish the prevalence of the defect or defects in their areas in order to demand the necessary test relevant to their place of work thereby setting the pertinent priority in that respect.
e.	There is an urgent need to identify the cause of the SPS phenotype.