This type of hemolytic anemia is associated with a variety of disorders; however, the mechanism leading to hemolysis is consistent. The fragmentation of RBCs results from their passage through abnormal arterioles: usually there is damage to the vessel wall or endothelial surface or fibrin has been deposited in the arteriole. Schistocytes are characteristically found on the peripheral blood smear.
THROMBOTIC THROMBOCYTOPENIC PURPURA (TTP) AND HEMOLYTIC UREMIC SYNDROME (HUS) These diseases will be discussed separately; however, TTP and HUS may well represent variant clinical presentations of a single disease. In selected patients, the specific diagnosis may be impossible to establish.
Thrombotic Thrombocytopenic Purpura TTP is a heterogeneous clinical syndrome characterized by this pentad of symptoms and signs:
1. Microangiopathic hemolytic anemia (MAHA) with characteristic schistocytes on the peripheral blood smear and a reticulocytosis
2. Thrombocytopenia with platelet counts ranging from 5000 to 100,000/pL
3. Renal abnormalities including renal insufficiency, azotemia, proteinuria, or hematuria
5. Neurologic abnormalities including headache, confusion, cranial nerve palsies, seizures, or coma
TTP has been diagnosed in patients of all ages but occurs most commonly between the ages 10 and 60. Women are affected more commonly than men. The course of the disease is typically acute and fulminant, lasting days to months, but it can be chronic and relapsing in 10 percent of patients. The overall survival rate is 80 percent, but the course is rapidly fatal in some patients. The majority of patients diagnosed with TTP have no apparent predisposing condition. In a small number of patients, TTP has been linked to genetic predisposition, pregnancy, immunologic diseases (SLE, rheumatoid arthritis, Sjogren's syndrome), or infections (viral, Mycoplasma pneumonia, subacute bacterial endocarditis, human immunodeficiency virus).
The pathogenesis of TTP is uncertain, but the presence of one or more platelet aggregating agents is likely responsible. Several abnormalities of the vascular endothelium and endothelial cell function have been implicated, including the release and presence of large von Willebrand multimers, decreased production of prostacyclin, inadequate fibrinolysis as a result of deficient tissue plasminogen activator (tPA) production, the presence of a platelet agglutinating protein, and deficient production of IgG molecules. Whatever the etiology, the result is the deposition of hyaline material within the lumina of capillaries and arterioles. These microthrombi are made of platelets and a small amount of fibrinlike material. These deposits may be found in any tissue but occur most frequently in the heart, brain, kidneys, pancreas, and adrenal glands.
The diagnosis of TTP is established clinically by the presence of the signs and symptoms listed above. Treatment should begin immediately based on these clinical and laboratory features. Biopsies are sometimes done of the gingiva, kidney, or bone marrow but are not essential to establish the diagnosis and should not delay therapy.
Clinically, the neurologic abnormalities are the most common presenting complaint, but hemorrhagic signs and symptoms and those referable to anemia are also common presentations. Laboratory studies will reflect the presence of MAHA with an anemia of variable degree (the hemoglobin will be less than 6 g/dL in one out of three patients), reticulocytosis, elevated indirect bilirubin, elevated LDH, negative Coombs' test, and the presence of schistocytes on the peripheral smear (the diagnosis of TTP is doubtful without schistocytes). Thrombocytopenia, reflective of the intravascular microthrombi, is often severe with the count less than 20,000/pL in 50 percent of patients. A mild leukocytosis with a left shift is common. The blood urea nitrogen (BUN) and creatinine are typically elevated to a mild to moderate degree. Urinalysis usually shows some degree of proteinuria and may show microscopic hematuria. Coagulation screening tests should be normal.
The salient features in the differential diagnosis of TTP are outlined in T§ble.,.214,:2,.
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