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: 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 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 and its look-alikes

The thrombotic thrombocytopenic purpura syndrome (TTP) can be mistaken for a number of other conditions, and it is important to diagnose correctly and treat appropriately. We describe the features of TTP that can help make a positive diagnosis and other conditions in the differential diagnosis with symptoms that can overlap and mimic those of TTR. We discuss TTP and its variants, hemolytic uremic syndrome, disseminated intravascular coagulation, heparin-induced thrombocytopenia, antiphospholipid syndrome, Evans syndrome, preeclampsia/eclampsia, HELLP syndrome, acute fatty liver of pregnancy, and multiorgan failure.     

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.     

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 acute pancreatitis

A 20 year old woman, admitted with acute pancreatitis, subsequently developed microangiopathic haemolytic anaemia, thrombocytopenia and mild neurological compromise. A diagnosis of thrombotic thrombocytopenic purpura (TTP) was made, and she was treated with plasma exchange leading to complete resolution of this condition. TTP is a rare multisystem disorder which may be life threatening if not treated promptly. The increasing recognition of acute pancreatitis as a potential aetiological factor offers new insights into the pathogenesis, diagnosis and treatment of TTP.     

Thrombotic thrombocytopenic purpura secondary to Streptococcus.

We describe a 16 year old female who developed thrombotic thrombocytopenic purpura (TTP) following infection due to Streptococcus. Initially presenting a fever and systemic upset she progressed to develop dialysis dependent acute renal failure, seizures, thrombocytopenia and a haemolytic anaemia--the pentad of features seen in TTP. Prior to the diagnosis she was found to have unexplained and previously undescribed MRI findings of diffuse increased signal intensity in the white matter of the left cerebellar hemisphere posteriorly and also increased signal intensity in the overlying cortex. She was commenced on plasmapheresis, and her anaemia, thrombocytopenia, creatinine and LDH all fully responded. In addition, she had no further seizures following plasmapheresis and has not relapsed to date. We review both the rare association of TTP and streptococcal infection, and the neuroradiological findings described in the literature. This is only the third case report describing TTP following streptococcal infection, and only the second in the era of plasmapheresis.     

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.     

Thrombotic thrombocytopenic purpura mimicking acute ischemic stroke

Thrombotic thrombocytopenic purpura (TTP) is an autoimmune disorder characterised by thrombocytopenia, haemolytic anemia, fluctuating neurological deficits, fever, and renal impairment. This case report is about a young man who presented with acute onset right sided paralysis, dysarthria, and central facial paralysis, suggestive of cerebrovascular accident, but eventually diagnosed as TTP. In addition, the clinical presentation of TTP is discussed and some teaching points for the emergency physicians are emphasised.     

血栓性血小板减少性紫癜误诊为Evans综合征

1　病例资料【例 1】　女 ,2 8岁。因头晕、尿色发黄、血小板减少 1周入院。入院前血小板由 81× 10 9/Ｌ降至 14×10 9/Ｌ ,伴皮肤发黄。查体 :皮肤巩膜黄染 ,肝脾未触及。辅助检查 :血白细胞 13 6× 10 9/Ｌ ,血红蛋白 6 9ｇ/Ｌ ,血小板 14× 10 9/Ｌ ,网织红细胞 33 2 % ;糖水试验、Ｈａｍ‘ｓ试验 ,抗人球免疫球蛋白直接及间接(Ｃｏｏｍｂｓ’)试验均为阴性 ;冷凝集试验未做 ;乳酸脱氢酶 4 5 2Ｕ/Ｌ ,总胆红素 4 3 9μｍｏｌ/Ｌ ,间接胆红素36 9μｍｏｌ/Ｌ ;骨髓细胞学检查示骨髓增生明显活跃 ,红系增生明显活跃 ,细胞着灰蓝色 ,大小…     

Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome.

Thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) are multisystemic disorders that are characterized by thrombocytopenia, microangiopathic hemolytic anemia, and ischemic manifestations, resulting from platelet agglutination in the arterial microvasculature. Until the introduction of plasma-based therapy, TTP was associated with a mortality rate greater than 90%. Current outcomes of TTP and HUS have improved dramatically with the use of plasma exchange, which should be initiated promptly at diagnosis. Recent evidence suggests that deficiency of a specific plasma protease responsible for the physiologic degradation of von Willebrand factor plays a pathogenic role in a substantial proportion of familial and acute idiopathic cases of TTP. Although multiple triggers, such as infection, drugs, cancer, chemotherapy, bone marrow transplantation, and pregnancy, are recognized, knowledge of the pathogenesis of TTP and HUS in relationship to these disorders remains incompletely understood and continues to evolve. While uncommon, TTP and HUS are of considerable clinical importance because of their abrupt onset, fulminant clinical course, and high morbidity and mortality in the absence of early recognition and treatment.     

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.