Ristocetin-Induced Platelet Aggregation (RIPA) and RIPA Mixing Studies

Methods Mol Biol. 2017:1646:473-494. doi: 10.1007/978-1-4939-7196-1_35.


Ristocetin-induced platelet aggregation (RIPA) is used as an in vitro test to determine the presence and integrity of the platelet glycoprotein (GP) Ibα-V-IX complex and von Willebrand factor (VWF) interaction and is usually performed using platelet-rich plasma (PRP). Impairment in the response of VWF/GPIbα-V-IX is measured with reference to several established concentrations of ristocetin and may indicate defects in VWF or in GPIbα-V-IX function. RIPA-based mixing studies comprise an additional approach to testing this interaction to help define whether defects identified by RIPA lie in VWF or in GPIbα-V-IX. For example, the correction of an abnormal RIPA trace after mixing PRP with normal plasma and rechallenging with ristocetin at 1.0 mg/mL suggests VWF function/quantity defect. RIPA mixing studies at lower doses of ristocetin (0.5 mg/mL) are recommended for discrimination of von Willebrand disease type 2B (VWD2B) from the rarer platelet-type (PT) VWD and for the phenotypic laboratory diagnosis of VWD2B. The demonstration of a plasma factor capable of inducing platelet aggregation at such low doses of ristocetin represents the hallmark for the phenotypic laboratory diagnosis of VWD2B. Moreover, since both VWD2B and PT-VWD may present with thrombocytopenia, RIPA-based mixing studies are also useful in thrombocytopenic patients in whom RIPA testing is difficult to assess.

Keywords: Light transmission aggregometry; Platelet aggregation; Platelet function testing; Ristocetin; von Willebrand.

MeSH terms

  • Adolescent
  • Adult
  • Blood Platelets / drug effects
  • Blood Platelets / metabolism*
  • Blood Specimen Collection / methods
  • Child
  • Child, Preschool
  • Equipment Design
  • Female
  • Humans
  • Light
  • Male
  • Middle Aged
  • Platelet Aggregation* / drug effects
  • Platelet Function Tests / instrumentation
  • Platelet Function Tests / methods*
  • Platelet Glycoprotein GPIb-IX Complex / metabolism*
  • Reference Values
  • Ristocetin / metabolism*
  • Young Adult
  • von Willebrand Diseases / diagnosis
  • von Willebrand Diseases / metabolism
  • von Willebrand Factor / metabolism*


  • Platelet Glycoprotein GPIb-IX Complex
  • von Willebrand Factor
  • Ristocetin