Intracranial Hemorrhage in a Patient with Osteogenesis Imperfecta Due to Inherited and Acquired Platelet Dysfunction.

A 42 year-old man with Osteogenesis Imperfecta (OI) had three episodes of spontaneous Subdural Hematoma (SH) after binge drinking. There is no remote history of abnormal bleeding or easy bruising despite multiple fractures. Medications included Aspirin (ASA). The first and second SH occurred within the preceding year and were treated conservatively. The third SH occurred while on ASA and drinking more than 500cc liquor/day. The Platelet Function Assay (PFA-100) was significantly abnormal (see table). After platelet transfusions the SH was surgically evacuated without complications. An MRA of the head showed no vascular abnormality. CBC, serum chemistries, PT, PTT, factor VIII and von Willebrand factor were normal. The patient stopped taking ASA, but continued to drink. The PFA-100, although abnormal, had improved. After a month-long alcohol abstinence his PFA-100 normalized. He has been without SH ever since. However the platelet aggregation study still shows a lack of second wave response to ADP.

Discussion: Both OI and ETOH are known factors of causing intrinsic platelet defect. The Framingham Offspring Study showed that alcohol consumption is inversely associated with both platelet activation and aggregation, particularly in men. ETOH is capable of inhibiting collagen induced platelet aggregation, secretion, arachidonate mobilization, and TXA2 formation. Also it has been suggested that intracellular Ca²⁺ homeostasis and aggregation in platelets are impaired by ethanol through the generation of H₂O₂ and oxidation of sulphydryl groups. OI causes vascular fragility and intrinsic platelet defect. In one study the most frequent abnormalities were increased capillary fragility (35%), decreased platelet retention (33%) and reduced factor VIII R:Ag (23%). Reduced ristocetin cofactor, deficient platelet aggregation induced by collagen and prolonged bleeding time were less common findings. The combination of vascular, platelet related and plasmatic defects may reflect that OI is a heterogeneous group of disorders with common clinical expression.

Conclusion: Patients with OI are at risk for intracranial bleeding due to vascular fragility and intrinsic platelet defect. Our patient had a normal PFA-100, off ASA and ETOH. The platelet aggregation study -a more sensitive test- was able to detect a platelet secretion defect in our patient. The abnormal platelet aggregation study was likely due to his OI, which never caused abnormal bleeding by itself. The additional affect of ASA and ETOH on his platelets led to recurrent episodes of SH. Many OI patients are on NSAID/ASA due to chronic bone pain. Special attention should be paid to alcohol abuse in this group of patients. Normal platelet counts and coagulation tests may not be sufficient to evaluate the risk of bleeding. We suggest performing a PFA-100 or a platelet aggregation study, when platelet dysfunction is suspected.