Thrombopoietin in Upshaw-Schulman Syndrome

To the Editor:

In 1960, Schulman et al1 reported on a patient with congenital thrombocytopenia and microangiopathic hemolytic anemia whose thrombocytopenia was transiently corrected by transfusion of normal plasma. These investigators speculated that the patient had a deficiency of thrombopoietic-stimulating factor, perhaps thrombopoietin (TPO). In 1978, a similar case was reported by Upshaw,2 who suggested that thrombocytopenia and microangiopathic hemolytic anemia were due to increased consumption of platelets, probably in the same manner as in chronic thrombocytopenic purpura. Later, we observed another patient with this disease, and found that, in addition to plasma, another plasma component also produced a transient correction of platelet count.3 4 

However, the question of the role TPO may play in this disease has never been addressed.

Recently, TPO, a ligand for the receptor encoded by the c-mpl proto-oncogene, has been purified, and it has been shown that TPO is involved in the regulation of megakaryocyte development and platelet production. It has become possible to accurately quantify the TPO level using the method of enzyme-linked immunosorbent assay.5 

We measured the TPO level of nine serum samples obtained from five patients from various parts of Japan who were suffering from this disease. Table 1 shows the TPO levels of all the samples we measured. Before plasma infusion, when the patients' platelet count was low (3.28 ± 1.93 × 10⁴/mm; mean ± SD) before plasma infusion (n = 9), the TPO level was as high (1.43 ± 0.89 fmol/mL) as that of normal adult serum (0.79 ± 0.35 fmol/mL).

We also had a chance to quantify TPO levels of four serum samples obtained when the patients' platelet counts increased after plasma infusion. Several days after plasma infusion, when the platelet count increased, the TPO level decreased to less than that of normal adult level (statistically not analyzed). The TPO levels of both the patients with idiopathic thrombocytopenic purpura (ITP; n = 12) and aplastic anemia (n = 7) are also included in the Table 1 as controls.

We conclude that the thrombocytopenia in these patients is not due to TPO deficiency. TPO levels are elevated appropriately in response to the degree and cause of thrombocytopenia and decrease as platelet count recovers after plasma infusion, indicating that TPO levels are regulated normally in these patients.