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Defective interaction between von Willebrand factor and platelet glycoprotein Ib--a familial study of peripheral
P Kauhanen1, J H Beer, R Lassila
1Wihuri Research Institute, Helsinki, Finland.
Insights
Patients with peripheral arterial occlusive disease (PAOD) show reduced platelet aggregation (RIPA) and increased D-dimer. This suggests altered hemostasis in PAOD, independent of platelet glycoprotein Ib function.
Area of Science:
- Cardiovascular Medicine
- Hematology
- Genetics
Background:
- Peripheral arterial occlusive disease (PAOD) is a condition affecting blood circulation.
- Hemostasis and platelet function play crucial roles in vascular diseases.
- Genetic factors may influence PAOD susceptibility and its associated hemostatic profile.
Purpose of the Study:
- To investigate hemostatic variables and platelet function in patients with symptomatic PAOD.
- To compare these parameters between PAOD patients and their healthy siblings within a genetic study context.
- To explore potential underlying mechanisms for altered platelet aggregation in PAOD.
Main Methods:
- Assessed hemostatic variables including D-dimer levels.
- Evaluated platelet function through ristocetin-induced maximal platelet aggregation (RIPA).
- Measured von Willebrand factor (vWF) related parameters and platelet glycoprotein Ib content.
Main Results:
- Elevated D-dimer levels were observed in the PAOD group compared to healthy siblings.
- Reduced RIPA was noted in PAOD patients at varying ristocetin concentrations.
- Key vWF parameters and platelet glycoprotein Ib content were comparable between groups, suggesting RIPA reduction is not due to altered vWF binding or receptor levels.
Conclusions:
- PAOD patients exhibit distinct alterations in hemostasis, characterized by increased D-dimer and impaired platelet aggregation.
- The observed reduction in RIPA is unlikely attributable to changes in platelet glycoprotein Ib or vWF binding affinity.
- These findings highlight potential hemostatic dysregulation in PAOD that warrants further investigation.
Abstract:
Hemostatic variables and platelet function were assessed as a part of a genetic study in 15 patients with symptomatic peripheral arterial occlusive disease (PAOD) and 15 healthy siblings from ten families. D-dimer, a degradation product of cross-linked fibrin, was increased in the PAOD group (mean +/- SD) (448 +/- 177 vs. 333 +/- 121 ng/ml, p < 0.05). Ristocetin-induced maximal platelet aggregation (RIPA) was reduced in the PAOD group in response to both a higher (0.75 mg/ml) (67 +/- 28 vs. 87 +/- 14%, p = 0.02) and a lower (0.55 or 0.60 mg/ml) (33 +/- 21 vs. 59 +/- 32%, p = 0.02) concentration of ristocetin. Accordingly, the rate of primary aggregation was smaller, and a larger threshold concentration of ristocetin was needed to cause aggregation. However, ristocetin cofactor activity, von Willebrand factor (vWF) antigen and its multimer distribution, plasma glycocalicin, platelet glycoprotein Ib content and the binding of vWF to frozen and thawed washed platelets were equal in both groups. Thus, the observed reduced RIPA in patients with PAOD is less likely to reflect a down-regulation or blunted binding affinity in the platelet surface glycoprotein Ib.