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Identification of platelet function defects by multi-parameter assessment of thrombus formation.

de Witt SM, Swieringa F, Cavill R, Lamers MM, van Kruchten R, Mastenbroek T, Baaten C, Coort S, Pugh N, Schulz A, Scharrer I, Jurk K, Zieger B, Clemetson KJ, Farndale RW, Heemskerk JW, Cosemans JM - Nat Commun (2014)

Bottom Line: Three types of thrombus formation can be identified with a predicted hierarchy of the following receptors: glycoprotein (GP)VI, C-type lectin-like receptor-2 (CLEC-2)>GPIb>α6β1, αIIbβ3>α2β1>CD36, α5β1, αvβ3.Application with patient blood reveals distinct abnormalities in thrombus formation in patients with severe combined immune deficiency, Glanzmann's thrombasthenia, Hermansky-Pudlak syndrome, May-Hegglin anomaly or grey platelet syndrome.We suggest this test may be useful for the diagnosis of patients with suspected bleeding disorders or a pro-thrombotic tendency.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Universiteitssingel 50, 6229 ER Maastricht, The Netherlands.

ABSTRACT
Assays measuring platelet aggregation (thrombus formation) at arterial shear rate mostly use collagen as only platelet-adhesive surface. Here we report a multi-surface and multi-parameter flow assay to characterize thrombus formation in whole blood from healthy subjects and patients with platelet function deficiencies. A systematic comparison is made of 52 adhesive surfaces with components activating the main platelet-adhesive receptors, and of eight output parameters reflecting distinct stages of thrombus formation. Three types of thrombus formation can be identified with a predicted hierarchy of the following receptors: glycoprotein (GP)VI, C-type lectin-like receptor-2 (CLEC-2)>GPIb>α6β1, αIIbβ3>α2β1>CD36, α5β1, αvβ3. Application with patient blood reveals distinct abnormalities in thrombus formation in patients with severe combined immune deficiency, Glanzmann's thrombasthenia, Hermansky-Pudlak syndrome, May-Hegglin anomaly or grey platelet syndrome. We suggest this test may be useful for the diagnosis of patients with suspected bleeding disorders or a pro-thrombotic tendency.

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Abnormal thrombus formation in blood from patients with rare platelet function defects.Whole blood from controls subjects or indicated patients was perfused over microspots of nine different surfaces (three microspots per run, 2–3 runs per surface). Surface numbering as in Fig. 1. (a) Heatmap of average parameters of thrombus formation for blood samples from control subjects (left), and blood samples from day control subjects (right). (b) Heatmaps and (c) subtraction heatmaps of parameters of thrombus formation for patients with indicated syndromes: SCID, May–Hegglin anomaly, grey platelet syndrome, Glanzmann’s thrombasthenia or Hermansky–Pudlak syndrome. *P<0.05 compared with control subjects (two-tailed Student’s t-test). (d) Significance map of parameters from a representative control subject and a day control subject, as well as from all patients. Colour key: red=deviating <mean−2 s.d.; green=deviating >mean+2 s.d., relative to normal values.
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f8: Abnormal thrombus formation in blood from patients with rare platelet function defects.Whole blood from controls subjects or indicated patients was perfused over microspots of nine different surfaces (three microspots per run, 2–3 runs per surface). Surface numbering as in Fig. 1. (a) Heatmap of average parameters of thrombus formation for blood samples from control subjects (left), and blood samples from day control subjects (right). (b) Heatmaps and (c) subtraction heatmaps of parameters of thrombus formation for patients with indicated syndromes: SCID, May–Hegglin anomaly, grey platelet syndrome, Glanzmann’s thrombasthenia or Hermansky–Pudlak syndrome. *P<0.05 compared with control subjects (two-tailed Student’s t-test). (d) Significance map of parameters from a representative control subject and a day control subject, as well as from all patients. Colour key: red=deviating <mean−2 s.d.; green=deviating >mean+2 s.d., relative to normal values.

Mentions: Thrombus formation was also assessed in blood from rare patients with established platelet function disorders. Heatmap mean data were generated for the control subjects and the individual patients under investigation (Fig. 8a,b). These data were further evaluated in subtraction heatmaps and significance maps (Fig. 8c,d).


Identification of platelet function defects by multi-parameter assessment of thrombus formation.

de Witt SM, Swieringa F, Cavill R, Lamers MM, van Kruchten R, Mastenbroek T, Baaten C, Coort S, Pugh N, Schulz A, Scharrer I, Jurk K, Zieger B, Clemetson KJ, Farndale RW, Heemskerk JW, Cosemans JM - Nat Commun (2014)

Abnormal thrombus formation in blood from patients with rare platelet function defects.Whole blood from controls subjects or indicated patients was perfused over microspots of nine different surfaces (three microspots per run, 2–3 runs per surface). Surface numbering as in Fig. 1. (a) Heatmap of average parameters of thrombus formation for blood samples from control subjects (left), and blood samples from day control subjects (right). (b) Heatmaps and (c) subtraction heatmaps of parameters of thrombus formation for patients with indicated syndromes: SCID, May–Hegglin anomaly, grey platelet syndrome, Glanzmann’s thrombasthenia or Hermansky–Pudlak syndrome. *P<0.05 compared with control subjects (two-tailed Student’s t-test). (d) Significance map of parameters from a representative control subject and a day control subject, as well as from all patients. Colour key: red=deviating <mean−2 s.d.; green=deviating >mean+2 s.d., relative to normal values.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4109023&req=5

f8: Abnormal thrombus formation in blood from patients with rare platelet function defects.Whole blood from controls subjects or indicated patients was perfused over microspots of nine different surfaces (three microspots per run, 2–3 runs per surface). Surface numbering as in Fig. 1. (a) Heatmap of average parameters of thrombus formation for blood samples from control subjects (left), and blood samples from day control subjects (right). (b) Heatmaps and (c) subtraction heatmaps of parameters of thrombus formation for patients with indicated syndromes: SCID, May–Hegglin anomaly, grey platelet syndrome, Glanzmann’s thrombasthenia or Hermansky–Pudlak syndrome. *P<0.05 compared with control subjects (two-tailed Student’s t-test). (d) Significance map of parameters from a representative control subject and a day control subject, as well as from all patients. Colour key: red=deviating <mean−2 s.d.; green=deviating >mean+2 s.d., relative to normal values.
Mentions: Thrombus formation was also assessed in blood from rare patients with established platelet function disorders. Heatmap mean data were generated for the control subjects and the individual patients under investigation (Fig. 8a,b). These data were further evaluated in subtraction heatmaps and significance maps (Fig. 8c,d).

Bottom Line: Three types of thrombus formation can be identified with a predicted hierarchy of the following receptors: glycoprotein (GP)VI, C-type lectin-like receptor-2 (CLEC-2)>GPIb>α6β1, αIIbβ3>α2β1>CD36, α5β1, αvβ3.Application with patient blood reveals distinct abnormalities in thrombus formation in patients with severe combined immune deficiency, Glanzmann's thrombasthenia, Hermansky-Pudlak syndrome, May-Hegglin anomaly or grey platelet syndrome.We suggest this test may be useful for the diagnosis of patients with suspected bleeding disorders or a pro-thrombotic tendency.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Universiteitssingel 50, 6229 ER Maastricht, The Netherlands.

ABSTRACT
Assays measuring platelet aggregation (thrombus formation) at arterial shear rate mostly use collagen as only platelet-adhesive surface. Here we report a multi-surface and multi-parameter flow assay to characterize thrombus formation in whole blood from healthy subjects and patients with platelet function deficiencies. A systematic comparison is made of 52 adhesive surfaces with components activating the main platelet-adhesive receptors, and of eight output parameters reflecting distinct stages of thrombus formation. Three types of thrombus formation can be identified with a predicted hierarchy of the following receptors: glycoprotein (GP)VI, C-type lectin-like receptor-2 (CLEC-2)>GPIb>α6β1, αIIbβ3>α2β1>CD36, α5β1, αvβ3. Application with patient blood reveals distinct abnormalities in thrombus formation in patients with severe combined immune deficiency, Glanzmann's thrombasthenia, Hermansky-Pudlak syndrome, May-Hegglin anomaly or grey platelet syndrome. We suggest this test may be useful for the diagnosis of patients with suspected bleeding disorders or a pro-thrombotic tendency.

Show MeSH
Related in: MedlinePlus