Thrombotic thrombocytopenic purpura presenting as bilateral flank pain and hematuria: a case report

Thrombotic thrombocytopenic purpura (TTP) is a rare disease whose incidence is now increasing. We present a case of a 37-year-old man who presented with bilateral flank pain and hematuria, subsequently diagnosed with TTP. Thrombotic thrombocytopenic purpura has classically been characterized by the pentad of fever, microangiopathic hemolytic anemia, neurologic symptoms, renal dysfunction, and thrombocytopenia. The pathogenesis of the disease has been a mystery until recently. We review the current literature regarding the pathophysiology and management of this disorder. Our discussion focuses on the importance of understanding this disease while considering the differential diagnosis of a patient presenting with anemia and thrombocytopenia because the common pitfall of rapidly administering platelets to a patient with TTP may lead to a disastrous outcome.     

Thrombotic thrombocytopenic purpura

This overview summarizes the history of thrombotic thrombocytopenic purpura (TTP) from its initial recognition in 1924 as a most often fatal disease to the discovery in 1997 of ADAMTS-13 deficiency as a major risk factor for acute disease manifestation. The cloning of the metalloprotease, ADAMTS-13, an essential regulator of the extremely adhesive unusually large von Willebrand factor (VWF) multimers secreted by endothelial cells, as well as ADAMTS-13 structure and function are reviewed. The complex, initially devised assays for ADAMTS-13 activity and the possible limitations of static in vitro assays are described. A new, simple assay using a recombinant 73-amino acid VWF peptide as substrate will hopefully be useful. Hereditary TTP caused by homozygous or double heterozygous ADAMTS-13 mutations and the nature of the mutations so far identified are discussed. Recognition of this condition by clinicians is of utmost importance, because it can be easily treated and--if untreated--frequently results in death. Acquired TTP is often but not always associated with severe, autoantibody-mediated ADAMTS-13 deficiency. The pathogenesis of cases without severe deficiency of the VWF-cleaving protease remains unknown, affected patients cannot be distinguished clinically from those with severely decreased ADAMTS-13 activity. Survivors of acute TTP, especially those with autoantibody-induced ADAMTS-13 deficiency, are at a high risk for relapse, as are patients with hereditary TTP. Patients with thrombotic microangiopathies (TMA) associated with hematopoietic stem cell transplantation, neo-plasia and several drugs, usually have normal or only moderately reduced ADAMTS-13 activity, with the exception of ticlopidine-induced TMA. Diarrhea-positive-hemolytic uremic syndrome (D+ HUS), mainly occurring in children is due to enterohemorrhagic Escherichia coli infection, and cases with atypical, D- HUS may be associated with factor H abnormalities. Treatment of acquired idiopathic TTP involves plasma exchange with fresh frozen plasma (FFP), and probably immunosuppression with corticosteroids is indicated. We believe that, at present, patients without severe acquired ADAMTS-13 deficiency should be treated with plasma exchange as well, until better strategies become available. Constitutional TTP can be treated by simple FFP infusion that rapidly reverses acute disease and--given prophylactically every 2-3 weeks--prevents relapses. There remains a large research agenda to improve diagnosis of TMA, gain further insight into the pathophysiology of the various TMA and to improve and possibly tailor the management of affected patients.     

Thrombotic thrombocytopenic purpura

This serious disorder of young adults is characterized by fever, hemolytic anemia, hemorrhagic signs, various neurologic abnormalities and renal dysfunction. Laboratory findings include a negative Coombs' test for hemolytic anemia, severe thrombocytopenia, and fragmented erythrocytes on the peripheral blood smear. Without treatment, mortality may exceed 80 percent. Early diagnosis and prompt therapy with high-dose corticosteroids and antiplatelet agents, as well as exchange plasmapheresis when indicated, bring about remission in 60 to 80 percent of patients.     

Thrombotic thrombocytopenic purpura (TTP) presenting as pancreatitis

Thrombotic thrombocytopenic purpura (TTP) is a rare clinical entity. It is a multi-systemic disorder characterized by a clinical pentad of thrombocytopenia, microangiopathic hemolytic anemia, diffuse and nonfocal neurologic symptoms, decreased renal function, and fever. Abdominal pain is an uncommon presenting symptom for TTP. Pancreatitis may occur from TTP or, in a few cases, may trigger TTP. The clinical diagnosis of TTP is generally difficult because there are many varied clinical presentations and the full expression of the pentad may be prolonged. However, once the diagnosis is suspected or confirmed, immediate plasmapherseis with plasma exchange must be performed to reduce the severe morbidity from neurologic disability.     

Thrombotic thrombocytopenic purpura: a hematological emergency

Background

Thrombotic thrombocytopenic purpura is a hematological emergency and diagnostic challenge. The critical determinant of outcome is timely diagnosis and treatment.

Objectives

Describe the pathophysiology, presentation, diagnosis, and treatment of thrombotic thrombocytopenic purpura.

Discussion

Thrombotic thrombocytopenic purpura has a varied presentation and a tendency to mimic several disorders. However, it may be at least provisionally diagnosed in the patient with thrombocytopenia and microangiopathic hemolytic anemia without alternate cause. The mainstay of treatment is immediate plasma exchange to be repeated until platelet count is stabilized. Adjuvant therapies include corticosteroids, rituximab, and cyclosporine.

Conclusion

It is essential for the emergency physician to be aware of thrombotic thrombocytopenic purpura’s range of presentations, diagnostic criteria, and treatment.     

神经系统症状为首发表现的血栓性血小板减少性紫癜1例报告

<正>血栓性血小板减少性紫癜(TTP)是血液科急重症,根据"五联征"或"三联征"诊断并不困难。但此病临床上少见,大多急骤起病、进展快、病情凶险、缺乏特异性临床症状和体征,容易误诊、漏诊。本病例以中枢神经系统症状为首发表现,首先考虑为脑膜脑炎或脑血管病等神经系统疾病,且患者合     

Thrombotic thrombocytopenic purpura associated with quetiapine

OBJECTIVE: To report a case of thrombotic thrombocytopenic purpura (TTP) caused by the antipsychotic quetiapine on 2 occasions in the same patient and review the hematologic adverse events associated with quetiapine. CASE SUMMARY: A 25-year-old African American male with a history of bipolar disorder was treated with quetiapine and developed thrombocytopenia, microangiopathic hemolytic anemia, and acute renal failure consistent with a diagnosis of TTP on 2 occasions 2 years apart. On each occasion, TTP was successfully treated with plasmapheresis. DISCUSSION: Many medications, including antibiotics, immunosuppressants, and antineoplastics, have been implicated as causative agents of TTP. Although, as of this writing, a review of the medical literature reveals no previous report of TTP associated with quetiapine, the Food and Drug Administration database of the Adverse Event Reporting System has compiled, as of this writing, 3 cases of TTP occurring in patients on quetiapine as their sole medication. In addition, this database has recorded other common hematologic adverse effects, including neutropenia and thrombocytopenia, that are possibly associated with quetiapine. In our patient, quetiapine-associated TTP presented within a few days after exposure to the drug, with early thrombocytopenia followed by delayed appearance (2-3 days) of microangiopathic hemolysis. CONCLUSIONS: An objective causality assessment suggests that quetiapine was the highly probable cause of TTP in this patient. Early recognition, discontinuation of the drug, and institution of plasmapheresis are paramount for prompt resolution of this life-threatening hematologic disorder.     

Thrombotic thrombocytopenic purpura: 2008 update

Thrombotic thrombocytopenic purpura (TTP) is a spectrum of syndromes characterized by thrombocytopenia and microangiopathic hemolytic anemia, manifested by an elevated blood lactate dehydrogenase (LDH) concentration and red blood cell fragments. It classically occurs in patients with a hereditary or acquired lack of ADAMTS13, a metalloproteinase that cleaves large multimers of von Willebrand factor. Other TTP-like syndromes, including TTP associated with pregnancy, organ transplantation, and certain medications, likely have different underlying causes and may require different treatment. Unless TTP is recognized promptly and treated aggressively, most patients die of it.     

Thrombotic thrombocytopenic purpura: a true haematological emergency

There are so few true haematological emergencies that they are often way down the list as a differential diagnosis. Those that do exist, however, can prove devastatingly fatal if left untreated and a case is presented of one such possible diagnosis, thrombotic thrombocytopenic purpura, which falls into the remit of many possible presenting conditions. Particularly prevalent in young adults, this condition must always be thought of in any patient presenting with confusion, renal impairment, fever or other neurological abnormalities.     

Thrombotic thrombocytopenic purpura in childhood

Thrombotic thrombocytopenic purpura (TTP) is a micro-angiopathic disease due to deficiency of the specific VWF cleaving protease (VWF-CP) ADAMTS13. The acquired form is caused by autoantibodies against VWF-CP, whereas mutations of the ADAMTS13 gene are responsible for inherited TTP. In childhood both forms exist with predominance of inherited TTP. The phenotype of TTP in childhood can be rather variable. Besides the classical clinical picture, abortive forms may occur that can delay the identification of patients at risk. The patients are frequently assumed to suffer from idiopathic thrombocytopenia (ITP) or Evans syndrome. Further efforts are necessary to accelerate correct diagnosis and to establish a risk-adapted prophylactic therapy.     

Thrombotic thrombocytopenic purpura: The israeli experience

Since 1985, 13 patients with thrombotic thrombocytopenic purpura (TTP) have been treated at the Hadassah Hospital. 1 patient died during the acute episode and eight had one or more relapses. Using a scoring system, developed in a previous report (Am J Med 1987; 83:437) to assess the severity of each episode, we found that 9 patients presented with severe TTP (score of 5–7) and four had milder symptoms (score 2–4). As reported previously, relapses were usually manifested by a milder clinical course, however 1 patient died during a relapse. The treatment for the initial TTP episode and the relapses consisted of steroids, platelet inhibitor drugs, vincristine and frequent plasma transfusions or exchanges and varied according to the severity of the disease. 4 patients underwent splenectomy. Two who failed to respond to conventional therapy underwent splenectomy and recovered following additional plasma therapy. The other two underwent splenectomy while in remission, in order to prevent frequent relapses. A significant favourable change in the course of their disease was observed.     

Thrombotic thrombocytopenic purpura precipitated by thyrotoxicosis

Thrombotic thrombocytopenic purpura (TTP) may be seen in association with autoimmune disorders such as immune hemolytic anemia and systemic lupus erythematosus, but rarely has it been associated with Graves' disease. We report one such case of a woman with new‐onset thyrotoxicosis caused by Graves' disease, who abruptly developed TTP, confirmed by low serum ADAMTS‐13 value. She had a dramatic response to plasma exchange, with remission of TTP. Definitive treatment with radioactive iodine resulted in euthyroidism and has prevented recurrence of TTP. J. Clin. Apheresis 27:265–266, 2012. © 2012 Wiley Periodicals, Inc.