USMLE Clotting deficiency question help

[tpsreport]

FA 2015 P. 397 notes that Glanzmann's thrombasthenia is the result of a defect in GpIIb/IIIa.

Ristocetin, which used to diagnose some bleeding disorders, is noted to basically act as vWF in an unknown fashion. Normal bleeding time with ristocetin diagnoses vWF deficiency.

The notes then say that agglutination does occur with ristocetin assay.

How does this work if ristocetin only affects vWF, which is only involved in platelet adhesion, whereas GpIIb/IIIa is solely platelet aggregation?

Any ideas would be welcome

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[CodeRedDew]

FA 2015 P. 397 notes that Glanzmann's thrombasthenia is the result of a defect in GpIIb/IIIa.

Ristocetin, which used to diagnose some bleeding disorders, is noted to basically act as vWF in an unknown fashion. Normal bleeding time with ristocetin diagnoses vWF deficiency.

The notes then say that agglutination does occur with ristocetin assay.

How does this work if ristocetin only affects vWF, which is only involved in platelet adhesion, whereas GpIIb/IIIa is solely platelet aggregation?

Any ideas would be welcome

So ristocetin actually induces platelet agglutination by essentially causing vWF to bind to platelet GPIb. Not sure exactly how it does this, but I just think of it as ristocetin bringing vWF and GPIb in close proximity to each other. Thus, the two diseases that lack either vWF or GPIb (Bernard-Soulier syndrome) will both have abnormal (ie. no agglutination) ristocetin test. Conversely, the receptor lost in Glanzman thrombasthenia has nothing to do with ristocetin; therefore, addition of ristocetin will cause agglutination because the platelets still have a functioning GPIb receptor. In a sense, the platelets are 'normal' in the eyes of ristocetin as the two things that it acts on (vWF and GPIb) are still functional.

 

[dfib slim]

FA 2015 P. 397 notes that Glanzmann's thrombasthenia is the result of a defect in GpIIb/IIIa.

Ristocetin, which used to diagnose some bleeding disorders, is noted to basically act as vWF in an unknown fashion. Normal bleeding time with ristocetin diagnoses vWF deficiency.

The notes then say that agglutination does occur with ristocetin assay.

How does this work if ristocetin only affects vWF, which is only involved in platelet adhesion, whereas GpIIb/IIIa is solely platelet aggregation?

Any ideas would be welcome

I think it goes like this.

No platelet agglutination with ristocetin cofactor assay in BSS because the vWF receptor GpIb is decreased.

Platelet aggregation with ristocetin cofactor assay in GT because the platelets have functioning GpIb so all the platelets stick together through a GpIb-vWF-GpIb bond.

 

[tpsreport]

Both of your answers make perfect sense. I was too focused on the platelets necessarily binding to endothelium (1 vWF to 1 GPIb of 1 platelet) and didn't think that they could just float around and bind to each other through vWF and GpIb using vWF as a focal point of adhesion.

Thanks guys!

I think it goes like this.

No platelet agglutination with ristocetin cofactor assay in BSS because the vWF receptor GpIb is decreased.

Platelet aggregation with ristocetin cofactor assay in GT because the platelets have functioning GpIb so all the platelets stick together through a GpIb-vWF-GpIb bond.

So ristocetin actually induces platelet agglutination by essentially causing vWF to bind to platelet GPIb. Not sure exactly how it does this, but I just think of it as ristocetin bringing vWF and GPIb in close proximity to each other. Thus, the two diseases that lack either vWF or GPIb (Bernard-Soulier syndrome) will both have abnormal (ie. no agglutination) ristocetin test. Conversely, the receptor lost in Glanzman thrombasthenia has nothing to do with ristocetin; therefore, addition of ristocetin will cause agglutination because the platelets still have a functioning GPIb receptor. In a sense, the platelets are 'normal' in the eyes of ristocetin as the two things that it acts on (vWF and GPIb) are still functional.