Upshaw-Schulman Syndrome Revisited: A Concept of Congenital Thrombotic Thrombocytopenic Purpura
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Upshaw-Schulman syndrome (USS) is a congenital bleeding disorder characterized by repeated episodes of thrombocytopenia and microangiopathic hemolytic anemia that respond to infusions of fresh frozen plasma. Inheritance of USS has been thought to be autosomal recessive, because 2 siblings in the same family are often affected but their parents are asymptomatic. Recently, chronic relapsing thrombotic thrombocytopenic purpura (CR-TTP), reported almost exclusively in adults, was shown to be caused by inherited or acquired deficiency in the activity of a plasma von Willebrand factor-cleaving protease (vWF-CPase).The pathogenesis of USS is unknown, and a relationship between CR-TTP and USS has not been reported. We studied 3 unrelated USS patients (ST, SY, and KI) who presented with severe indirect neonatal hyperbilirubimenia. All 3 patients had undetectable vWF-CPase activity, and the inhibitors to vWF-CPase were all negative. In their parents with no clinical symptoms, vWF-CPase activities as a percentage of control samples (mother/father) were 17/20 for ST, 60/45 for SY, and 36/5.6 for KI. Thus, USS and vWF-CPase activity appear to be coinherited as autosomal recessive traits. Transfusion of fresh frozen plasma in 2 patients (ST and SY) resulted in the expected maximal increment of approximately 7% to 8% in vWF-CPase activity at 1 to 4 hours, but the levels became less than 3% within 2 days. After this decrease, platelet counts increased, plateaued in the normal range at 10 to 12 days, and declined thereafter. Thus, the 2 to 3 weeks of therapeutic benefit from plasma infusions will be discussed in relation to the intravascular lifetime of vWF-CPase.
- Schulman I, Pierce M, Likens A, Currimbhoy Z. Studies on thrombopoiesis. I.A factor in normal human plasma required for platelet production; chronic thrombocytopenia due to its deficiency.Blood. 1960;14:943–957.
- Upshaw JD. Congenital deficiency of a factor in normal plasma that reverses microangiopathic hemolysis and thrombocytopenia.N Engl J Med. 1978;298:1350–1352.
- Rennard S, Abe S. Decreased cold-insoluble globulin in congenital thrombocytopenia (Upshaw-Schulman syndrome).N Engl J Med. 1979;300:368.
- Koizumi S, Miura M, Yamagami M, Horita N, Taniguchi N, Migita S. Upshaw-Schulman syndrome and fibronectin (cold-insoluble globulin).N Engl J Med. 1981;305:1284–1285.
- Goodnough LT, Saito H, Ratnoff OD. Fibronectin levels in congenital thrombocytopenia: Schulman’s syndrome.N Engl J Med. 1982;306:938–939.
- Moake JL, Rudy CK, Troll JH, et al. Unusually large plasma factor VIII: von Willebrand factor multimers in chronic relapsing thrombotic thrombocytopenic purpura.N Engl J Med. 1982;307:1432–1435.
- Miura M, Koizumi S, Nakamura K, et al. Efficiency of several plasma components in a young boy with chronic thrombocytopenia and hemolytic anemia who responds repeatedly to normal plasma infusions.Am J Hematol. 1984;17:307–319. CrossRef
- Hara T, Kitano A, Kajiwara T, Kondo T, Sakai K, Hamasaki Y. Factor VIII concentrate-responsive thrombocytopenia, hemolytic anemia, and nephropathy: evidence that factor VIII:von Willebrand factor is involved in its pathogenesis.Am J Ped Hematol Oncol. 1986;8:324–328. CrossRef
- Miura M, Koizumi S, Miyazaki H. Thrombopoietin in Upshaw-Schulman syndrome.Blood. 1997;89:4663–4664.
- Furlan M, Robles R, Lammle B. Partial purification and characterization of a protease from human plasma cleaving von Willebrand factor to fragments produced by in vivo proteolysis.Blood. 1996;87:4223–4234.
- Tsai H-M. Physiological cleavage of von Willebrand factor by a plasma protease is dependent on its conformation and requires calcium ion.Blood. 1996;87:4235–4244.
- Furlan M, Robles R, Solenthaler M, Wassmer M, Sandoz P, Lämmle B. Deficient activity of von Willebrand factor-cleaving protease in chronic relapsing thrombotic thrombocytopenic purpura.Blood. 1997;89:3097–3103.
- Fujimura Y, Titani K, Holland L, et al. von Willebrand factor. A reduced and alkylated 52/48-kDa fragment beginning at amino acid residue 449 contains the domain interacting with platelet glycoprotein Ib.J Biol Chem. 1986;261:381–385.
- Shima M, Fujimura Y, Nishiyama T, et al. ABO blood group genotype and plasma von Willebrand factor in normal individuals.Vox Sanguinis. 1995;68:236–240. CrossRef
- Ruggeri ZM, Zimmerman TS. Variant von Willebrand’s disease: characterization of two subtypes by analysis of multimeric composition of factor VIII/von Willebrand factor in plasma and platelets.J Clin Invest. 1980;65:1318–1325. CrossRef
- Budde U, Schneppenheim R, Plendl H, Dent J, Ruggeri ZM, Zimmerman TS. Luminographic detection of von Willebrand factor multimers in agarose gels and on nitrocellulose membranes.Thromb Haemost. 1990;63:312–315.
- Miura S, Sakurai Y, Takatsuka H, et al. Total inhibition of high shear stress induced platelet aggregation by homodimeric von Willebrand factor A1-loop fragments.Br J Haematol. 1999;105:1092–1100. CrossRef
- Furlan M, Robles R, Morselli B, Sandoz P, Lämmle B. Recovery and half-life of von Willebrand factor-cleaving protease after plasma therapy in patients with thrombotic thrombocytopenic purpura.Thromb Haemost. 1999;81:8–13.
- Furlan M, Robles R, Galbusera M, et al. von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome.N Engl J Med. 1998;339:1578–1584. CrossRef
- Tsai H-M, Lian EC-Y. Antibodies to von Willebrand factor-cleaving protease in acute thrombotic thrombocytopenic purpura.N Engl J Med. 1998;339:1585–1594. CrossRef
- Kasper CK, Aledort LM, Counts RB, et al. A more uniform measurement of factor VIII inhibitors.Thromb Diathesis Haemorrhagica. 1975;34:869–872.
- Konno M, Yoshioka A, Takase T, Imai T. Partial clinical improvement in Upshaw-Schulman syndrome following prostacyclin infusion.Acta Paediatr Japonica. 1995;37:97–100.
- Rabkin Y, Fradin Z, Zeidman A, Schwartz A, Cohen A, Mittelman M. Chronic relapsing thrombocytopenic purpura with severe neurological manifestations and full recovery.Int J Hematol. 2000;71:184–187.
- Moake JL, Turner NA, Stathopoulos NA, Nolasco LH, Hellums JD. Involvement of large plasma von Willebrand factor (vWF) multimers and unusually large vWF forms derived from endothelial cells in shear stress-induced platelet aggregation.J Clin Invest. 1986;78:1456–1461. CrossRef
- Ruggeri ZM. von Willebrand factor.J Clin Invest, 1997;99:559–564. CrossRef
- Siedlecki CA, Lestini BJ, Kottke-Marchant K, Eppell SJ, Wilson, DL. Shear-dependent changes in the three-dimensional structure of human von Willebrand factor.Blood. 1996;88:2939–2950.
- Upshaw-Schulman Syndrome Revisited: A Concept of Congenital Thrombotic Thrombocytopenic Purpura
International Journal of Hematology
Volume 74, Issue 1 , pp 101-108
- Cover Date
- Print ISSN
- Online ISSN
- Additional Links
- Upshaw-Schulman syndrome
- Chronic relapsing TTP
- von Willebrand factor-cleaving protease
- Fresh frozen plasma
- Industry Sectors
- Author Affiliations
- 1. Departments of Pediatrics, Nara Medical University, Nara
- 2. Health Science, Nara Medical University, Nara
- 3. Department of Pediatrics, Sapporo Kosei General Hospital, Sapporo
- 4. Department of Pediatrics, Yodogawa Christian Hospital, Osaka
- 5. Institute of Comprehensive Medical Science, Fujita Health University, Aichi, Japan
- 6. Blood Transfusion Medicine, Nara Medical University, Nara