Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (414 page)

   
Under no circumstances should the clinician wait for results of ADAMTS13 levels or its antibodies before starting therapy when other criteria for TTP are present
. Extremely low plasma levels of ADAMTS13 (<5–10%) are characteristic for TTP but not entirely specific since they are found occasionally in non-TTP microangiopathic anemia cases. The absence of ADAMTS13 at the time of diagnosis is predictive of relapsing episodes in nearly half of cases.

   In thrombotic microangiopathies associated with allogeneic stem cell transplantation, chemotherapy and other drugs, as well as in HUS (see below), the levels of the protease are in most cases normal. Because 94% to 97% of idiopathic TTP cases are acquired and due to anti-ADAMTS13 antibodies, the antibodies assay should be performed at the same time with the measurement of the enzyme.

HUS

   CBC, LDH, haptoglobin, indirect bilirubin, direct Coombs and coagulation results are similar to those of TTP.

   Creatinine is very elevated at presentation in most cases.

   Urinalysis may show proteinuria and red cell casts.

   ADAMTS13 is normal in most cases of HUS.

Suggested Readings

George JN. How I treat patients with thrombotic thrombocytopenic purpura: 2010.
Blood.
2010;116:4060–4069.

Kremer Hovinga JA, Lammle B. Role of ADAMTS13 in the pathogenesis, diagnosis, and treatment of thrombotic thrombocytopenic purpura.
Hematology Am Soc Hematol Educ Program.
2012;2012:610–616.

MISCELLANEOUS DISORDERS

IRON OVERLOAD DISORDERS (IOD) AND HEREDITARY HEMOCHROMATOSIS (HH)

   Definition

The term IOD refers to patients with increased iron stores resulting from iron supply that exceeds the body’s ability to eliminate it. Due to iron toxicity, its excess results in tissue damage (liver cirrhosis often followed by hepatocellular carcinoma, diabetes, and cardiomyopathy). IOD may be primary, commonly hereditary, or secondary (acquired). The most common form of primary IOD in North America and Western Europe is HH.

Hereditary (primary) hemochromatosis

   HH is an HLA-linked autosomal recessive defect, caused by increased duodenal absorption of iron from dietary sources, leading to excess iron deposition in various organs. HH is the result of an abnormal gene present in 10% of the Caucasian population (see below under Genetic studies). The manifest disease, in contrast with the genotypical or biochemical phenotype, is quite rare. Excess iron is toxic to cells due to excess production of free radicals and the Fenton reaction.

   Other genetic forms of hemochromatosis are juvenile hereditary hemochromatosis, neonatal hemochromatosis aceruloplasminemia, mutations in transferrin receptor-22 or ferroportin-1, and African iron overload (combined hereditary increased absorption and excess intake, seen particularly in Bantu

Secondary hemochromatosis

   Increased, long-term intake of iron medication

   Anemias with ineffective erythropoiesis and/or extravascular hemolysis (especially if associated with multiple transfusions): sickle cell anemia, β-thalassemia major, aplastic anemia, myelodysplastic syndromes