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At a glance

A rare syndrome characterized by congenital microangiopathic hemolytic anemia, thrombotic thrombocytopenic purpura, and response to fresh plasma infusion. Neonatal onset and frequent relapses are typical.

Synonyms

Congenital Microangiopathic Hemolytic Anemia; Schulman-Upshaw Syndrome; Deficiency of Upshaw Factor; Familial Thrombotic Thrombocytopenic Purpura.

History

First described by Jefferson D. Upshaw, an American hematologist, in 1978.

Incidence

Rare; estimated incidence 3 to 11 per 1,000,000.

Genetic inheritance

Autosomal recessive.

Pathophysiology

Thrombotic thrombocytopenic purpura is caused by mutations in the ADAMTS13 (A Disintegrin And Metalloproteinase with ThromboSpondin type I motif, 13) gene located on 9q34. Thrombocythemia is caused by deficiency in ADAMST13 metalloproteinase which reduces the metamers of the von Willebrand factor resulting in unusually large multimers of von Willebrand factor. This creates a high shear stress and heterozygous thrombotic microangiopathy with hemolytic anemia (schistocytes), thrombocytopenia, and focal organ involvement (Hemolytic-Uremic Syndrome).

Diagnosis

Based on evidence of thrombocytopenia, microangiopathic hemolysis, ADAMTS-13 activity, and end organ injury. Dramatic response to fresh plasma therapy.

Clinical aspects

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. Corticosteroids or splenectomy has no effect. When asymptomatic, patient has a compensated hemolytic state with variable reticulocytosis and low-normal hematocrit levels. Often it is 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.

Precautions before anesthesia

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 uncommon).

Anesthetic considerations

Because of the low platelet count, regional anesthesia, particularly perimedullar blockade, should be avoided, as should nasogastric tubes and nasal intubation.

Pharmacological implications

Salicylates are best avoided considering the risk of defective platelets or thrombocytopenia.

References

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George  JN, Nester  CM: Syndromes of thrombotic microangiopathy. NEJM 371:654, 2014.  [PubMed: 25119611]
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Saha  M, McDaniel  JK, Zheng  XL: Thrombotic thrombocytopenic purpura: Pathogenesis, diagnosis and potential novel therapeutics. J Thromb Haemost 15:1889, 2017.  [PubMed: 28662310]
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Upshaw  JD: Congenital deficiency of a factor in normal plasma that reverses microangiopathic hemolysis and thrombocytopenia. N Engl J Med 298:1350, 1978.  [PubMed: 651994]
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Yagi  H, Konno  M, Kinoshita  S,  et al: Plasma of patients with Upshaw-Schulman syndrome, a ...

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