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Thrombotic Thrombocytopenic Purpura

Differential Diagnosis

Based on the clinical hematologist's findings, he confirmed the presence of blood in the urine (hematuria), fragmented red blood cells (schistocytes), decreased hemoglobin, elevated lactate dehydrogenase (LDH), and low platelets (thrombocytopenia). All of these findings are consistent with a hemolytic episode. The differential diagnoses includes:

• Thrombotic thrombocytopenic purpura (TTP)
• Immune thrombocytopenia purpura (ITP)
• Autoimmune hemolytic anemia
• Hemolytic uremic syndrome (HUS)
• Pregnancy, eclampsia
• Disseminated intravascular coagulation (DIC)
• Septicemia with DIC
• Systemic lupus erythematosus (SLE)
• Scleroderma
• Paroxysmal nocturnal hemoglobinuria (PNH)

Immune thrombocytopenia purpura generally lacks anemia and is dominated by petechial lesions and mucosal hemorrhage. The Coombs test is positive in autoimmune hemolytic anemia and is also frequently positive in SLE. In addition, leukopenia is commonly seen in SLE. Characteristic laboratory findings in PNH are anemia, leukopenia, and thrombocytopenia, also known as pancytopenia. The PT/APTT are increased in DIC. Also, in DIC the fibrinogen is usually decreased. It should be pointed out that no single test is diagnostic of DIC; however, in the appropriate clinical setting, patient history and type of bleeding, and laboratory data can ensure a diagnosis of DIC.

Some tests that may help exclude DIC are:

• D-Dimer test: D-Dimer is a fibrin degradation product generated by plasmin lysis of cross-linked fibrin clots. The presence of this fragment is an indication of fibrin clot formation and secondary clot lysis. It is a highly reliable test for diagnosis of DIC.
• Protamine test: Detects fibrin monomers in plasma. This test should be positive in patients with DIC; however, fifteen to twenty percent of patients with DIC may have a negative result.
• Thrombin time: Measures the conversion of fibrinogen to fibrin. Thrombin time is usually prolonged.
• Plasminogen: Plasminogen is the inactive precursor of plasmin. Plasminogen may be depressed as the result of ongoing fibrinolysis.
• Fibrinopeptide A: Thrombin is the only enzyme that releases the specific peptides, fibrinopeptide A and B, from the fibrinogen molecule. Patients with DIC have elevated levels of fibrinopeptide A; however, the determination of fibrinopeptide A level by itself is not specific for DIC.
• B-Beta 15-42: A relatively recent development has been the recognition of an early cleavage product of the B-beta chain of the fibrinogen dimer. Elevation of both fibrinopeptide A and B-beta 15-42 is a strong indicator of DIC, rather than of primary fibrinolysis.

Hemolytic uremic syndrome was also ruled out (Table 4).

Modified from Harmening DH. Clinical hematology and fundamentals of hemostasis. 3rd ed. Philadelphia: F. A. Davis; 1997, 519.

Diagnosis

A diagnosis of TTP was made based on the patient's clinical presentation and the supportive laboratory data. Patients with TTP initially present with nonspecific symptoms of malaise, weakness, and fatigue. TTP patients usually present with fever, abdominal pain and bleeding as a result of severe thrombocytopenia. Hemolysis is associated with an increase in serum LDH, total bilirubin, reticulocytosis, and the presence of spherocytes and fragmented red cells on the smear. Prothrombin time (PT), activated partial thromboplastin time (APTT), and fibrinogen levels are usually normal in patients with TTP, although FDPs may be slightly elevated.