Thrombotic Thrombocytopenia Purpura

Blood Detective

University of California, Irvine hematologist Dr. Jae Chang specializes in blood cell analysis to diagnose obscure, complex disorders that stymie or get missed by many physicians. A writer of poetry and avid reader of mystery novels, his research across 30 years includes thrombotic thrombocytopenic purpura, or TTP, a rare disease that destroys red blood cells that normally deliver oxygen throughout the body. Among other things, TTP causes kidney or brain failure. The National Institutes of Health estimates TTP affects 1 in every 250,000 Americans.

DI: Tell us about one of your TTP patients.

JC: One man came to the UCI medical center with severe breathing problems. Other doctors determined he had acute respiratory distress syndrome, which is usually fatal if not corrected quickly, perhaps within two days. Its cause can be hard to pinpoint. When I studied this man’s blood cells, something in them reminded me of another case in which TTP had caused respiratory distress. So we administered plasma exchange, the standard therapy for TTP. After many weeks in the hospital, he left TTP-free. It’s a great joy helping critically ill patients. We cannot save them all because the clock works against us.

DI: Patients worldwide seek your help. Would you elaborate?

JC: I met a 29-year-old Honduran woman who came to the United States for treatment of sickle cell disease. She consulted me as a last resort. Back in Honduras, her anemia already had developed, and her chest pain was consistent with sickle cell. In California, another physician administered blood transfusions along with medication for chest and joint pain before I met her. The transfusions proved an overload of iron, so she was treated for that, too. Her prognosis and psyche were poor.

When I met her, she looked almost normal, whereas someone with advanced sickle cell often has osteoporosis and shortness of breath. Still, many diseases leave footprints in the blood. This woman didn’t have as many sickle cells in her blood as I expected. There was anemia in her blood count, and it appeared she inherited a gene abnormality from her mother that is typical of sickle cell. However, she didn’t have the second gene abnormality for sickle cell that I expected but instead evidence of hereditary persistence of fetal hemoglobin, which she likely got from her father.

Her blood disorder was actually much milder than originally feared, and she didn’t need so many transfusions going forward. If this patient manages her issues well, she might have a normal life expectancy. This summer, a woman with hemolytic anemia came from Korea to see me. She’d had the condition for more than 20 years. Within two days, I was pretty close to diagnosing the problem and hope to help her.

A Case of Thrombotic Thrombocytopenia Purpura Associated with ...

Abstract

Thrombotic thrombocytopenia purpura (TTP) caused by a deficiency in ADAMTS-13 activity is considered to involve a subset of thrombotic microangiopathy (TMA). Although concept of TTP is included under the umbrella of TMA, discrimination of TTP from TMA is occasionally difficult in an autoimmune disorder. Herein, we report a case with TTP associated with systemic lupus erythematosus (SLE). In this case, it was difficult to discriminate TTP from TMA and the measurement of ADAMTS-13 activity was useful for obtaining an accurate diagnosis. SLE patients having thrombocytopenia in complication with anemia should be considered a monitoring of ADAMTS-13 activity even though the patients lacked symptoms of TTP related to the microvascular coagulation.

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening syndrome first described by Moschocowitz in 1924 [ 1 ]. TTP is clinically characterized by five typical syndromes: thrombocytopenia with platelet consumption, hemolytic anemia characterized by schistocytes, renal impairment, neurological abnormalities, and fever. The classic pentad described above is observed in as few as 40% of TTP patients [ 2 ], and the clinical course of the syndrome is usually rapid, therefore, an accurate diagnosis and immediate treatment including plasma exchange is necessary [ 3 ]. Von Wiilebrand factor-(vWF)-specific metalloprotease, a disintegrin-like and metalloprotease with thrombospondin type 1 motif-13 (ADAMTS-13) is known to play an important role in the pathogenesis of TTP [ 4 – 6 ]. A severe deficiency of ADAMTS-13 activity prevents the physiological processing of large vWF multimers which can lead to a strong platelet aggregation, and leads to the formation of microthrombosis in terminal arterioles and capillaries. Besides TTP, microthrombosis without a deficiency in ADAMTS-13 activity can also be associated with other diseases such as hemolytic uremic syndrome (HUS), various autoimmune diseases, cytotoxic drugs, human immunodeficiency virus (HIV), malignancies, disseminating intravascular coagulopathy (DIC), and pre-eclampsia [ 7 ]. Recently, these pathological conditions characterized by microthrombosis including TTP, have been classified as thrombotic microangiopathies (TMA). In autoimmune disorders, TMA occasionally occurs in systemic lupus erythematosus (SLE), antiphospholipid antibody syndrome (APS) [ 8 , 9 ], and in many rare autoimmune disorders [ 7 ]. Rigorous classification of TMA is important to decide on the appropriate therapy. In particular, the combination of TTP and SLE has been reported to show a worse prognosis than SLE or idiopathic TTP alone [ 10 ], therefore, an accurate diagnosis and an immediate treatment are required.

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