An Overview of the Laboratory’s Role in the Diagnosis and Treatment of Thrombotic Thrombocytopenic Purpura

INTRODUCTION

Thrombotic thrombocytopenic purpura (TTP) is a hematologic disorder that results in microthrombi forming in the small capillaries of the circulatory system. Although sometimes confused with other hematologic disorders, TTP is classically seen with thrombocytopenia, microangiopathic hemolytic anemia (MAHA), fragmented erythrocytes, neurological defect, and fever. TTP can be rapidly fatal, requiring quick assessment of symptoms and start of treatment to reduce mortality.

LABORATORY’S ROLE

Laboratory confirmation of TTP is determined by a profound decrease in ADAMTS13 enzyme activity. The follow-up to a decreased ADAMTS13 activity assay is to detect autoantibodies to ADAMTS13, confirming the diagnosis of acquired TTP.² Additional laboratory testing includes a complete blood count, clinical chemistry panel, and urinalysis. Specific testing includes lactic acid dehydrogenase, haptoglobin, bilirubin, prothrombin time and activated partial thromboplastin time, and other indicators of hemolysis.² The hemolysis in TTP arises from increased shear stress on red blood cells in arterioles and capillaries narrowed by microthrombi.

TTP is still considered a life-threatening disease with a mortality rate of 10%–20%. Even though TTP is a serious hematologic emergency that is almost always fatal in untreated cases, an understanding of its pathophysiology can lead to successful treatment strategies resulting in improved patient management and outcomes.

Aside from routine laboratory findings, TTP is a disease that is classified by abnormal functioning of the ADAMTS13 protease. ADAMTS13 protease impairment can be caused by genetic mutations at the gene level or through autoantibodies that are formed within the circulation. Congenital mutations account for about 5%–10% of the TTP population, whereas the acquired version is more common. The acquired version of TTP is due to inhibitory and noninhibitory autoantibodies that affect the ADAMTS13 protease. Both congenital and acquired TTP are treated through transfusion therapy with therapeutic plasma exchange (TPE). TPE is used to remove the autoantibodies and any mutated ADAMTS13 proteases in the circulation, while providing the addition of normal functioning ADAMTS13 to the circulation. TPE is removal and retention of plasma through an apheresis machine that allows all cellular products to be returned to the circulation.⁶ TPE was first employed in 1952, and by the 1970s, it was a multiuse treatment for many different diseases. The efficiency of TPE depends on the plasma volume that is being removed and pathogenic substrate (immune globulin G and immune globulin M antibodies in TTP). One volume exchange is equivalent to 65% of the initial component removed with 75%–85% substrate removal within two TPE procedures.⁶

CASE STUDY

This Focus Series is designed to provide a comprehensive review of TTP for the laboratory scientist. The following articles will provide in-depth understanding of the etiology, pathogenesis, immunology, laboratory findings, and treatment of TTP. This case study is the review of diagnosis and treatment of a 40-year-old female who presented to the emergency department. The original laboratory findings can be seen in Table 1. The presented results, which are analyzed in the following Focus article, demonstrate why prompt and accurate diagnosis and treatment are needed in cases of TTP.