A very rare syndrome characterized by congenital
microangiopathic hemolytic anemia, thrombotic thrombocytopenic purpura, and
response to fresh plasma infusion. Neonatal onset and frequent relapses are
Congenital Microangiopathic Hemolytic Anemia;
Schulman-Upshaw Syndrome; Deficiency of Upshaw Factor; Familial Thrombotic
First described by Jefferson D. Upshaw, an American
hematologist, in 1978.
Phenotype may be identical to thrombotic
thrombocytopenic purpura, which is caused by mutations in the ADAMTS13 gene
located on 9q34. Thrombocythemia is caused by a combination of the presence
of plasma factor VIII and von Willebrand factor (UL-VWFMs), platelets, and
high shear stress generated in the microcirculation. Prostacyclin
(PGI2) may be partly involved.
Based on congenital Upshaw factor deficiency, distorted
and fragmented circulating red cells, and cold insoluble globulin
Characterized by frequent episodes of severe
thrombocytopenia and severe anemia (microangiopathic hemolytic anemia). It is
often in association with a clinically detectable infection or a
precipitating stress. A dramatic response to the administration of whole blood or plasma alone.
Corticosteroids or splenectomy has no effect. When asymptomatic, patient has
a compensated hemolytic state with variable reticulocytosis and low-normal
hematocrit levels. Often associated with radioulnar hypoplasia and
lobster-claw deformity. Petechial rash may be present with episodic fever
and glomerulopathy. Preeclampsia is frequent. Treatment is definitely the administration of
plasma and platelet transfusion.
A complete cell blood count (especially hemoglobin and
platelet count) must be obtained before and after surgery. One must ensure that
fresh-frozen plasma is available if blood transfusion is anticipated. Check
renal function (glomerulopathy with hematuria and proteinuria is not
Because of the low platelet count,
regional anesthesia, particularly perimedullar blockade, should be avoided,
as should nasogastric tubes and nasal intubation.
Salicylates are best avoided
considering the risk of defective platelets or thrombocytopenia.
Konno M, Yoshioka A, Takase T, et al: Partial clinical improvement in
Upshaw-Schulman syndrome following prostacyclin infusion. Acta Paediatr Jpn 37(1):97, 1995.
Upshaw JD: Congenital deficiency of a factor in normal plasma that reverses
microangiopathic hemolysis and thrombocytopenia. N Engl J Med
Yagi H, Konno M, Kinoshita S, et al: Plasma of patients with Upshaw-Schulman
syndrome, a congenital deficiency of von Willebrand factor-cleaving protease
activity, enhances the aggregation of normal platelets under high shear
stress. Br J Haematol 115(4):991, 2001.