Thrombotic thrombocytopenic purpura (TTP) / Hemolytic-uremic syndrome (HUS)

Abstract:
The thrombotic thrombocytopenic purpura (TTP, Morbus Moschcowitz) and the hemolytic uremic syndrome (HUS) are closely related acute clinical syndromes with microangiopathic hemolytic anemia (MAHA) and thrombocytopenia. Besides the hematological alterations, there are renal function disorder, neurological findings, and fever of varying degree. Classical HUS occurs mostly in children and is preceded by hemorrhagic diarrhea caused by verotoxin-producing enteropathogenic bacteria such as E. coli O157:H7. Classical TTP in adults is caused b a deficiency of ADAMTS13 (von Willebrand factor (vWF)-cleaving protease). Often, an auto-antibody against ADAMTS13 can be demonstrated and thus the autoimmune cause of the disease. Phylogenetically, there is microvascular thrombosis (microangiopathy) with vWF-platelet-thrombi (in TTP), or fibrinogen-platelet-thrombi (in HUS). Microangiopathy leads to the consumption of platelets (thrombocytopenia) and the destruction of erythrocytes (intravascular hemolysis, schistocytes).

Clinical picture:

Classical TTP of the adult is a very rare, acquired, and fulminant disease that is mostly lethal if not treated in time. The typical picture with MAHA, thrombocytopenia, renal failure, changing neurological findings and fever is today seen only rarely because of early diagnosis and treatment. The therapy consists in plasma exchange (plasmapheresis) and substitution with fresh frozen plasma (contains ADAMTS13). An immediate onset of therapy is imperative in order to reduce morbidity and mortality.

A recurrent type of TTP in younger people is caused by a hereditary deficiency of ADAMTS13 (Upshaw-Schulman syndrome).
HUS is typically caused by Shigella-toxin producing enteral bacteria such as enterohemorrhagic Escherichia coli (EHEC). Therefore, it typically occurs together with diarrhea.

Hematology:

The blood picture of TTP is characterized by the presence of schistocytes as sign of microangiopathy. Usually, the number of schistocytes is high (above 1%). in rare cases, only few schistocytes are found. Massive hemolysis leads to polychromasia and the early release of normoblasts. Additionally, marked to severe thrombocytopenia occurs. Signs of hemolysis (high bilirubin,reticulocytosis, low haptoglobin) are positive. Typical are high values of LDH, as manifestation of hemolysis as well as tissue damage. Measurement of ADAMTS13 confirms the diagnosis in classical TTP (very low values) and is helpful for therapy follow-up.

Bone marrow:
The diagnosis of TTP and/or HUS is an emergency. A bone marrow examination is not necessary. In the case of a therapy-refractory or otherwise untypical course, a bone marrow aspiration is recommend to exclude secondary causes. Usually, the bone marrow shows increased erythropoiesis and megakaryocytopoiesis.