Our July 2022 Quick Question asked, “What VWD subtype is identified using the reduced concentration RIPA test?” We received 30 votes. Here are our answers:
- VWD Type 1: 10% [3]
- VWD Type 1C: 0
- VWD Subtype 2A: 3%
- VWD Subtype 2B: 87%
- VWD Subtype 2M: 0
- VWD Subtype 2N: 0
- VWD Type 3: 0
Few of us were misled by this question. The ristocetin-induced platelet aggregation [RIPA] test that uses patient platelets and reduced ristocetin concentration is the traditional test we use to identify VWD Subtype 2B, where the abnormality is caused by a gain-of-function mutation that raises the VWF avidity for its platelet receptor site.
VWD Type 1 is a quantitative VWF deficiency that is identified using the VWF:Ag test or one of the VWF activity assays, such as the time-honored VWF:RCo, the VWF:CB, VWF:GPIbR, or the VWF:GPIbM.
Subtype 1C hasn’t appeared in Fritsma Factor before. It is a quantitative VWF deficiency in which the VWF secretion rate is near-normal, but its plasma half-life is reduced to 1–3 hours. Subtype 1C is identified using molecular tests.
VWD Subtype 2M is caused by a qualitative VWF disorder in which VWF possesses reduced avidity for its platelet receptor site, and Subtype 2N [Normandy] is a mutation in the factor VIII binding site that reduces factor VIII adhesion, causing hemophilia-like symtoms in both males and females.
Just for completeness, low
Just for completeness, low dose RIPA may also be positive in platelet-type (‘PT-‘, or ‘pseudo-‘) VWD, where the VWF platelet receptor (GPIb) expresses a gain of function mutation that binds normal VWF ‘spontaneously.’ Of course, there is contention about the name, since the defect is not in VWF, so how can this be a form of ‘VWD‘. There is also an ISTH survey in progress related to ‘renaming’ of PT/pseudo-VWD to better reflect the platelet origin. Although both 2B and PT–VWD can both be identified using low dose RIPA, you need to perform either RIPA-mixing studies, or genetic testing of VWF and platelet GPIb to differentiate them; differentiation is important since therapy differs–you don’t give VWF concentrates to patients with PT–VWD! PT–VWD appears to be much less common than 2B VWD. If anyone is interested in RIPA/RIPA-mixing, I have written a protocol with my Argentinean colleague and friend Juan Pablo Frontroth (Frontroth JP, Favaloro EJ. 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. PubMed PMID: 28804849.). Happy to share a copy if you send me an email; if you want my email address, look me up in PubMed.