Platelet Signaling Disorder

Platelet Signaling Disorder
Jan 29, 2019 2:21pm

A patient experiences chronic moderate bleeding from a surgical site and venipuncture sites over 48 months. The bleeds consistently require intervention. There is no epistaxis and minor bruising. The only diagnostic laboratory result is impaired aggregation epinephrine and ADP agonists, and absence of arachidonic acid-induced aggregation. All other hemostasis and hematology results report within their respective reference intervals. The results appear to indicate a platelet signal transduction (signalling) disorder, or "aspirin-like disorder (ALD)." Platelet signaling disorders are often described, but seldom defined.

I (Geo) invite anecdotes or documentation that describe the prevalence and mechanisms of platelet signaling disorders. While these aggregometry results seem to point to lesions in the eicosanoid synthesis pathway, do we have definitive evidence? What enzymes are affected? Phopholipase C? Cyclooxygenase? Thromboxane synthase? Alternatively, are we really looking for defective receptor sites? Finally, has anyone described an acquired signalling disorder?

To support this discussion, I've attached a well-referenced comprehensive review of platelet disorders. Rao, AK. Inherited defects in platelet signaling mechanisms. J Thromb Haemostasis 2003; 1: 671–81. Please use the Comments section below or email george@fritsmafactor.com to describe your experience with platelet signaling disorders.

1 Comment

A patient experiences chronic moderate bleeding from a surgical site and venipuncture sites over 48 months. The bleeds consistently require intervention. There is no epistaxis and minor bruising. The only diagnostic laboratory result is impaired aggregation epinephrine and ADP agonists, and absence of arachidonic acid-induced aggregation. All other hemostasis and hematology results report within their respective reference intervals. The results appear to indicate a platelet signal transduction (signalling) disorder, or "aspirin-like disorder (ALD)." Platelet signaling disorders are often described, but seldom defined.

I (Geo) invite anecdotes or documentation that describe the prevalence and mechanisms of platelet signaling disorders. While these aggregometry results seem to point to lesions in the eicosanoid synthesis pathway, do we have definitive evidence? What enzymes are affected? Phopholipase C? Cyclooxygenase? Thromboxane synthase? Alternatively, are we really looking for defective receptor sites? Finally, has anyone described an acquired signalling disorder?

To support this discussion, I've attached a well-referenced comprehensive review of platelet disorders. Rao, AK. Inherited defects in platelet signaling mechanisms. J Thromb Haemostasis 2003; 1: 671–81. Please use the Comments section below or email george@fritsmafactor.com to describe your experience with platelet signaling disorders.

By Dr. Vadim Kostousov
Feb 1, 2019 10:59am
Hello, George,
I just would like to share published/reported experience of others in this field:

"Clinical and laboratory phenotypes associated with the aspirin-like defect: a study in 17 unrelated families" https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2141.2008.07468.x

"Clinical and laboratory phenotype associated with the aspirin-like defect - commentary" https://onlinelibrary.wiley.com/doi/epdf/10.1111/j.1365-2141.2009.07950.x

"Congenital Aspirin-like Defect As a Result of Autosomal Recessive Variants in PTGS1" https://ash.confex.com/ash/2018/webprogram/Paper118958.html

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