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[Figure][1] A 5-year-old girl was treated for 4 years based on a diagnosis of immune thrombocytopenia (ITP). When she presented for a second opinion, she met all criteria for ITP except that inspection of her peripheral blood smear showed large platelets with a complete lack of granulation

Abstract 1097 The immature platelet fraction (IPF) is a useful parameter indicating thrombopoietic activity to differentiate the causes of thrombocytopenia. We previously reported that the percentage of IPF (%IPF) is negatively correlated to the platelet count among ITP patients, and not among myelodysplastic syndrome (MDS) patients. We also noticed that some MDS patients exhibited extremely high %IPF values, which were dissociated from the percentages of reticulated platelets (%RP) measured by flow cytometry. Such discrepancies were also observed in hereditary macrothrombocytopenias, which are sometimes difficult to be distinguished from ITP, because ITP also exhibits increased number of reticulated platelets in a slightly larger size. Once misdiagnosed, a hereditary macrothrombocytopenia patient might be subjected to an invasive treatment such as splenectomy. In order to avoid such mistreatments, a clear marker to differentiate macrothrombocytopenia is desperately needed. In this study, we investigated the IPF values of 16 individuals from 12 families with various hereditary macrothrombocytopenia in order to clarify whether the IPF could be a useful marker to distinguish macrothrombocytopenia from ITP, and examined the IPF during EDTA aggregation and cold-storage to elucidate how platelet size may affect the IPF value. The IPF values were about 5 times higher in MYH9 disorders (%IPF 48.0 ± 1.8) and about 1.5 times higher in other macrothrombocytopenias (%IPF 17.0 ± 2.2) than immune thrombocytopenic patients with similar platelet counts (%IPF 9.3 ± 0.4). These results suggested that the platelet size can affect the IPF value. However it still remains the possibility that some factors specific to these macrothrombocytopenias other than the platelet size might make an influence on the IPF, because the characteristic of large platelets in hereditary macrothrombocytopenia has not been fully understood, and no one knows whether large platelets are functionally identical to normal platelets except for the size. In order to exclude the possibility, we next examined the changes of IPF values during EDTA aggregation and cold-storage. The IPF was significantly increased during storage in a time dependent manner along with forming platelet clumps. The IPF was strongly influenced by a few tiny platelet aggregates rather than other platelet indices, such as mean platelet volume (MPV), platelet-large cell ratio (P-LCR) and platelet distribution width (PDW). In conclusion, the IPF is susceptible to the platelet size, and could be a useful parameter for screening of macrothrombocytopenia from ITP. Disclosures: No relevant conflicts of interest to declare.

A form of von Willebrand's disease has been described with enhanced ristocetin-induced platelet aggregation and anodal migration of the factor VIII/von Willebrand factor protein (type IIb). We studied two families with this form of von Willebrand's disease and macrothrombocytopenia. We have found that these platelets bind more of the normal and intermediate-sized multimers of the factor VIII/von Willebrand factor than normal platelets. Analysis of the binding data show an increased affinity of these vWd platelets for the factor VIII/von Willebrand factor. These findings are consistent with an increased number of platelet receptors, which, either by their native topography or migration on the platelet surface, bind factor VIII/von Willebrand factor protein with greater affinity than normal platelets, platelets of other vWd patients, and large platelets of other etiologies.

Five female members of a family manifesting a dominantly inherited bleeding disorder were investigated for coagulation and platelet abnormalities. A long bleeding time, mild thrombocytopenia, large platelets, low platelet factor-3 activity (PF-3), and low factor VIII levels were found in the proband. Long bleeding times, low PF-3, and low factor VIII levels were found in various combinations in the four other family members studied. PF-3 was abnormal by three techniques in the proband and could be corrected by adding ADP. Her platelets and those of one other member did not aggregate when exposed to collagen. The proband’s platelets did not release ADP on collagen exposure. The severity of bleeding was proportional to the number of laboratory abnormalities in the individual’s studied. The findings in this family overlap both hereditary thrombopathia and von Willebrand’s disease and were quite variable between family members. It appears that there exists a spectrum of dominant hereditary bleeding disorders with abnormalities in the platelets or factor VIII levels or both, with variable expressivity in family members.