Familial bleeding disorder associated with deficiencies in platelet signal processing and glycoproteins.
Aggregation responses to low concentrations of ADP, epinephrine, collagen and cationophore A23187 in platelets from two family members with marked bleeding tendencies were virtually absent, whereas shape change with ADP was normal. The contribution to factor X activation by collagen-treated platelets was markedly decreased. Glycoproteins IIb and III were also significantly reduced. The patients' platelets had normal stores of secretable constituents, but secretion of adenine nucleotides and acid hydrolases in response to low concentrations of thrombin and A23187 was drastically reduced compared to normal platelets; secretion of platelet factor 4 was normal. Agonist concentrations that normally produce maximal responses induced only partial aggregation and secretion in the patients' platelets. After prelabelling with [3H]arachidonate thrombin caused less changes in the [3H]phosphatidylinositol, [3H]phosphatidylcholine and free [3H]arachidonate in platelets from the patients than in platelets from normals. We conclude that the patients' platelets have an impairment in part of the signal processing mechanism that is common for all agonists and responses. This platelet abnormality, which has a superficial resemblance to thrombasthenia, represents a hitherto undescribed qualitative platelet disorder.
Holmsen
H
H
Thrombosis Research Center, Temple University School of Medicine, Philadelphia, PA 19140.
Walsh
P N
PN
Koike
K
K
Murphy
S
S
Holme
S
S
Johnson
M M
MM
Dangelmaier
C A
CA
Egan
J J
JJ
Benzel
J E
JE
Tuszynski
G P
GP
D000244:Adenosine Diphosphate / Q000097:blood; D000255:Adenosine Triphosphate / Q000097:blood; D001780:Blood Coagulation Tests; D001791:Blood Platelet Disorders / Q000097:blood / Q000235:genetics*; D001792:Blood Platelets / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D010375:Pedigree; D010743:Phospholipids / Q000097:blood; D010974:Platelet Aggregation; D010980:Platelet Membrane Glycoproteins / Q000172:deficiency*
D010743:Phospholipids; D010980:Platelet Membrane Glycoproteins; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate