Introduction 20 11 1 1 Fig. 1 a b c  1 1 37 2 Fig. 2 Electron microscopy (original magnification ×22,500) of platelets showing the dense tubular system (DTS), microtubules (MT), open canalicular system (OCS), alpha granules (G), glycogen (Gly) and the dense bodies (DB)  1 13 35 1 Table 1 Syndromic and non-syndromic platelet defects and the implicated genes according to the defective platelet pathway Type of platelet defect Isolated platelet disorders Disorders including a platelet defect Disorders studied by functional platelet assays Adhesion and cytoskeletal defects Glanzmann thrombastenia May-Hegglin anomaly, Fechtner syndrome, Epstein syndrome, and Sebastian syndrome Neurological disorders as bipolar disorder, schizophrenia, depression, autism  Prolonged bleeding time All: macrothrombocytopenia, prolonged bleeding time   No other clinical problems All: leucocyte inclusions, Epstein,Fechtner: nephritis, deafness, cataracts   ITGB3  ITGA2 MYH9   Bernard-Soulier Syndrome Duchenne Muscular Dystrophy   Macrothrombocytopenia, prolonged bleeding time Prolonged bleeding after surgery   No other clinical problems Muscle degeneration   GPIbα  GPIbβ  GPIX DMD  G protein signalling defects ADP P2Y12 receptor Inducible Gsα hyperfunction syndrome Subclinical platelet defect  Prolonged bleeding time Prolonged bleeding time after trauma   No other clinical problems Brachydactyly, increased alkaline phosphatase and neurological or growth retardation   P2Y12 XLαs   Thromboxane TXA2 receptor PACAP overexpression   Prolonged bleeding time Prolonged bleeding time   No other clinical problems Mental retardation and hypogonadism   TXA2R PACAP  Secretion defects Gray platelet disorder Hermansky Pudlack disease Neurological defect?  Prolonged bleeding time Prolonged bleeding time   No other clinical problems Albinism, lysosomal defect   ? HSP 1–8   Delta storage Pool disease Chediak Higashi disease   Prolonged bleeding time Prolonged bleeding time   No other clinical problems Albinism, immunological lethal defect   ? LYST   ITGB3  ITGA2  GPIbα  GPIbß  GPIX  P2Y12  TXASR  MYH9  DMD  PACAP  HSP 1–8  LYST When considering type of platelet tests 13 40 2 36 36 Table 2 Clinical presentation of coagulation and platelet-based bleeding disorders Clinical symptoms Disorders of coagulation Disorders of platelets Petechiae, epistaxis Rare Characteristic Superficial ecchymoses Common: large and solitary Characteristic: small and multiple Bleeding from superficial cuts and bruises Minimal Persistant: often profuse Delayed bleeding Common Rare Deep dissecting hematomas Characteristic Rare Hemarthrosis Characteristic Rare Functional and morphological platelet studies in patients with mainly a neurological, metabolic or another clinical problem but no obvious bleeding problem are usually not performed for diagnostic purposes but rather for research aims. In such patients, novel insights are expected to result from the platelet research studies, which are still preliminary today but in the future hopefully will help to better define when to ask for what type of platelet tests in a given patient. Thrombopathies 30 31 35 ITGA2 ITGB3 1 22 22 36 15 14 1 2 3 42 37 32 1 12 Human disorders comprising a platelet defect 29 38 26 1 6 7 18 27 4 5 43 1 . 1 8 9 17 10 25 36 44 16 21 Human disorders examined by functional and morphological platelet assays 33 2 24 34 19 23 28 39 41 Conclusions Platelet research is an expanding field originally studying isolated thrombopathies caused by the imbalance between thrombosis and hemostasis but more recently being able to bring novel insights in our understanding of human pathology in other clinical disciplines such as neurology, endocrinology and metabolic diseases. Platelets are easily accessible cells, and different techniques are possible to study platelet function and morphology under basal and activated conditions. Defects in platelet adhesion, G protein signalling and secretion can result from mutations in platelet-specific genes leading to isolated thrombopathies or from mutations in widely expressed genes leading to broader clinical phenotype including a platelet defect. In addition to using platelet research for diagnostic purposes, these platelet functional and morphological studies can also be used for research aims. From the close collaboration between clinicians of different disciplines, geneticists and the functional platelet research unit, novel insights in the pathogenesis of different human disorders are to be expected in the near future by using this strategy.