Cocaine‐induced microangiopathic hemolytic anemia mimicking idiopathic thrombotic thrombocytopenic purpura: A case report and review of the literature

Our understanding of the pathogenesis of idiopathic thrombotic thrombocytopenic purpura (TTP) has increased, but remains incomplete, particularly with respect to cases of suspected TTP that are either unresponsive to therapeutic plasma exchange (TPE) or have normal ADAMTS13 (a d isintegrin‐like a nd m etalloprotease with t hrombos pondin type 1 motif 13 ) activity. A 53‐year‐old woman presented with severe anemia (hemoglobin 1.8 g/dL) and clinical and laboratory findings consistent with TTP in conjunction with acute cocaine use. The patient was treated with TPE until the pre‐treatment ADAMTS13 activity was reported as normal without evidence of an inhibitor. TPE was stopped and the patient continued to improve without treatment. This patient's microangiopathic hemolytic anemia (MAHA) appeared to be secondary to cocaine use. The proposed pathogenesis is likely a combination of cocaine‐induced vasoconstriction, vascular damage, platelet activation, and procoagulation. This is the fifth published report of cocaine‐induced MAHA and to our knowledge the first with ADAMTS13 testing. J. Clin. Apheresis 29:284–289, 2014. © 2014 Wiley Periodicals, Inc.     

Thrombotic thrombocytopenic purpura and pregnancy: report of four cases and literature review

Thrombotic thrombocytopenic purpura (TTP) is a severe life-threatening hematological disorder affecting the microcirculation of multiple organ systems. Infection, pregnancy, cancer, drugs, and surgery are frequently associated with the initial episodes and relapses. Women who are either pregnant or in the postpartum period make up 10-25% of TTP patients, suggesting the interrelationship between TTP and pregnancy. The introduction of aggressive treatment with plasma transfusion and plasmapheresis has improved maternal and fetal survival rates. We report four cases of pregnancy-related TTP, describing the clinical course of patients, including response to therapy and pregnancy outcomes. Three out of four (75%) patients were treated by daily single session of plasmapheresis for a period ranged between 3 and 23 days. One patient had complete response to treatment with no sequelae, the second patient had resistant disease and died due to multiorgan failure, while the third patient had complete response after 2 episodes of TTP, which was complicated by intrauterine fetal growth retardation and death. Review of the previously reported cases of pregnancy-related TTP and the current treatment options for this rare condition are discussed also.     

Myocardial injury in HIV‐associated thrombotic thrombocytopenic purpura (TTP)

Thrombotic thrombocytopenic purpura (TTP) has been associated with human immunodeficiency virus (HIV) infection. With the high prevalence of HIV in sub‐Saharan Africa, HIV‐associated TTP is the most common form of this disease seen in the South African population. Several case reports describe myocardial infarction in HIV‐negative TTP patients. The case of the first HIV‐positive patient who presented with clinical signs and symptoms of TTP and myocardial injury is reported in this study. A patient with fragmentation haemolysis and thrombocytopenia presented with angina. Risk factors for ischaemic heart disease were absent. An electrocardiogram (EKG) revealed ST‐segment elevation and a significantly raised Troponin T level. The patient's HIV test was positive and a diagnosis of myocardial injury with HIV‐associated TTP was made. The patient was treated with plasma infusion and steroid therapy. Due to poor response, the therapy was changed to plasma exchange. The patient recovered fully and subsequent coronary angiography revealed normal coronary vessels. Treatment of myocardial infarction in TTP is controversial, but the treatment cornerstone should remain plasma infusion or plasma exchange. As patients are often young and do not have the classical risk factors of ischaemic heart disease, a high level of suspicion and routine exclusion of myocardial ischaemia in these patients are advised.     

An insidious presentation of thrombotic thrombocytopenic purpura: A case report and brief literature review

Thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy with an estimated incidence of 11 cases/million population per year. Early treatment is essential and is curative in this disease where lack of treatment results in 90% mortality. We describe an atypical case of a patient with TTP who presented to the Emergency Department for headache, and was found to have thrombocytopenia but only mild anemia that was explained by another disease process. Case: A 44-year-old female presented to the Emergency Department for worsening headache and weakness over the last week. She had no fever and no focal neurological deficits but was pale and complained of severe headache. A blood test showed her to be anemic and thrombocytopenic. She explained that she had been having prolonged heavy menses over the last year. She was treated with blood and platelet transfusions, and seen by the Gynecology service who treated her for uterine fibroids after which she was discharged. She returned 1 week later with the same complaint, and was found to have a stable hemoglobin level but recurrence of thrombocytopenia. A TTP diagnosis was entertained and the workup confirmed it. The patient was treated with plasmapheresis and discharged home with no sequalae. Conclusion: Emergency physicians should keep TTP in mind when approaching cases of thrombocytopenia with mild anemia, even if an alternative diagnosis exists.     

Transfusion-related acute lung injury: a thrombotic thrombocytopenic purpura treatment-associated case report and concise review

Blood products are frequently required immediately prior to, during, or just after an apheresis procedure. Transfusion-related acute lung injury (TRALI) is now the leading cause of transfusion-related mortality, surpassing ABO-incompatible hemolytic reactions. The reported incidence of TRALI varies but is estimated at 1 in 5,000 transfusions. The true incidence could be higher because of under-reporting and under-diagnosis. Plasma is the most frequently implicated blood product. While the pathogenesis of TRALI appears multifactorial, one contributing factor seems to be donor antibodies to cognate recipient neutrophil antigens. Biologically active neutrophil-priming substances may also play a role. New diagnostic criteria have recently been proposed to aid in the diagnosis of TRALI. We report a thrombotic thrombocytopenic purpura (TTP) treatment-associated case of TRALI and review the history, pathogenesis, diagnosis and management of this syndrome. Current risk reduction strategies are also discussed.     

血栓性血小板减少性紫癜误诊1例

患者,女,19岁,因“发热、腹泻3d,伴牙龈出血、右肩右髋部出血点1d”,至我院急诊就诊。患者入院前3d无明显诱因出现腹泻、呕吐、高热、腹痛,腹泻初为水样便,量多,后逐渐为黑色便,发热体温最高达40℃。在家自服去痛片、阿莫西林、安乃近等药。入院前1d出现牙龈出血,伴右肩、右髋部出血点。来诊时急查化验示血常规：     

Coexistence of thrombotic thrombocytopenic purpura and immune thrombocytopenic purpura in an Asian woman: a case report

A 33-year-old Chinese woman with a history of immune thrombocytopenic purpura presented with heavy menstrual bleeding. She was found to have thrombocytopenia, plasma ADAMTS13 activity of 0%, and positivity for the plasma ADAMTS13 inhibitor. She was diagnosed with the coexistence of thrombotic thrombocytopenic purpura and immune thrombocytopenic purpura. The patient was treated by plasmapheresis, a glucocorticoid, and rituximab. Her platelet level returned to normal, and she was discharged 28 days after admission. The number of plasmapheresis sessions and the timing of rituximab administration may be the key aspects of management of patients with thrombotic thrombocytopenic purpura who have underlying immune dysfunction caused by diseases such as immune thrombocytopenic purpura.     

ASFA Category IV becomes Category I: Idiopathic thrombotic thrombocytopenic purpura in a patient with presumed gemcitabine‐induced thrombotic microangiopathy

In the implementation of American Society for Apheresis national guidelines, the decision for therapeutic plasma exchange may be confounded by a clinical presentation that fits both a Category I and IV designation. We report the case of a 45‐year‐old female who presented with concern for a Category IV disorder, gemcitabine‐induced thrombotic microangiopathy, and was ultimately diagnosed with a Category I disorder, idiopathic thrombotic thrombocytopenic purpura. This case highlights the importance of ruling out idiopathic TTP by a thorough evaluation for ADAMTS13 activity and inhibitor, even when an alternate thrombotic microangiopathy diagnosis may be likely.     

Efficacy of eculizumab in severe ADAMTS13-deficient thrombotic thrombocytopenic purpura (TTP) refractory to standard therapies

Thrombotic thrombocytopenic purpura (TTP) is a rare microangiopathic hemolytic anemia (MAHA) defined by mechanical hemolytic anemia, severe thrombocytopenia, and systemic visceral ischemia due to systemic platelet-rich microthrombi. Forty percent of patients with autoimmune TTP experience one or multiple relapses. Patients with refractory TTP are currently managed by corticosteroids, twice-daily PEX, and the anti-CD20 monoclonal antibody rituximab. Herein, we report two cases of severe TTP, refractory to those standard agents. On the basis of the fact that in cases of severe TTP the classical complement pathway is activated, and that the alternative pathway is also involved, both patients underwent eculizumab (anti-C5 monoclonal antibody) therapy. We observed prompt hematological and organ system responses to the eculizumab and the recovery of plasma ADAMTS-13 activity in both cases. Moreover, the fact that both patients discontinued eculizumab, maintaining the response, emphasizes the possibility of its usefulness for limited treatment periods. In conclusion, the diagnostic and therapeutic algorithm in TTP appears complicated by increasing evidence of complement involvement and the eculizumab seems to be a potential agent for refractory patients.     

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 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.     

United States thrombotic thrombocytopenic purpura apheresis study group (US TTP ASG): Multicenter survey and retrospective analysis of current efficacy of therapeutic plasma exchange

Thrombotic thrombocytopenic purpura (TTP) remains enigmatic from the perspective of its etiology, pathophysiology, and treatment. Once recognized, the accepted standard of care for TTP is daily therapeutic plasma exchange (TPE). However, the diversity in TPE treatment protocols has made comparisons of clinical research between institutions difficult. This study strived to assess the current practice of TPE in order to provide direction for prospective controlled clinical trials. Twenty large apheresis centers within the United States comprising the US TTP ASG responded to a survey to establish the current status of TPE in TTP. A retrospective analysis from data provided by 14 of 20 centers included 115 initial presentations of primary TTP with an overall mortality rate of 10% and relapse rate of 37%. The majority of deaths (58%) occurred within 48 hours of presentation. Variation in therapeutic targets (platelet count [plt] and serum LDH) and the number of plasma volumes exchanged per procedure did not affect the relapse rate. Initial plt and LDH were not predictive of mortality. Response, relapse, and mortality rates with the combination of 5% albumin for the initial 50% of TPE followed by plasma for the final 50% of TPE as replacement were comparable or possibly better than plasma-only replacement strategies. Forty percent of centers routinely used a TPE taper; however, there was no statistical difference in relapse rates comparing the taper and non-taper sub-groups. By controlling for adjunctive modalities such as steroids and anti-platelet agents, it is hoped that future prospective clinical trials may optimize the role of TPE in TTP, minimize patient exposure to blood products and procedures, shorten the clinical course of TTP, and reduce mortality. J. Clin. Apheresis 13:133–141, 1998. © 1998 Wiley-Liss, Inc.     

Thrombotic thrombocytopenic purpura associated with pesticides: A report of 4 cases and literature review

Thrombotic thrombocytopenic purpura (TTP) is a disease characterized by the presence of microangiopathic hemolytic anemia (MAHA) and thrombocytopenia, caused by the congenital or acquired decrease of the enzyme activity which degrades unusual large vWF multimers. There is no identifiable cause in half of the acquired TTP cases. Herein, we report four possible pesticide-related cases with decreased ADAMTS13 enzyme activity, increased titer of ADAMTS13 inhibitor and typical clinical and laboratory presentation.     

Endocarditis‐induced thrombotic thrombocytopenic purpura mimicking preeclampsia: A case report

TTP, Preeclampsia have similar manifestations in pregnancy. Establishing the right diagnosis is essential as the treatment is different. Endocarditis‐induced TTP should be suspected when neurological symptoms, thrombocytopenia are present.     

Thrombotic thrombocytopenic purpura: report of fourteen cases--occurrence during pregnancy and response to plasma exchange

Thrombotic thrombocytopenic purpura (TTP), a syndrome of diverse etiology probably related to factors regulating platelet-vessel wall interaction, is predominantly a disorder of women. We report our experience with 14 patients in an 11-year period. Thirteen were female and aged between 25-69 years. Four were postmenopausal, and of the nine premenopausal women three were pregnant, one was immediately postpartum, and three were taking estrogen-containing oral contraceptives. A review of the literature confirms the two to one female/male preponderance and that TTP is reported in 56 women who are pregnant or recently postpartum. While this association with possible hormonal events has been noted, it has previously received little comment. We stress the similarity between TTP and some occurrences of preeclamptic toxemia, and that this may suggest not only a common etiology but that therapeutic attempts should be similar. While no single therapeutic modality is universally successful, our experience is that plasma exchange is the most effective, with five of seven patients so-treated obtaining prolonged remission; four of five patients responded to splenectomy and corticosteroids, but one died of infection postoperatively. Five patients, including two treated exclusively with antiplatelet aggregating agents, died without achieving remission. The frequency of successful therapy is not changed by the concurrent pregnancy, but the fetal loss is high. There does seem to be an increased risk of recurrence of TTP in a subsequent pregnancy, and this might be considered when counseling premenopausal patients who have achieved remission of TTP.     

Fremanezumab plus plasmapheresis in a patient with chronic migraine and myasthenia gravis: Case report of an effective treatment

A patient with chronic migraine and generalized myasthenia gravis was concurrently treated with fremanezumab and with therapeutic plasmapheresis (PEX). Fremanezumab was dosed right after a PEX session, or in the midpoint between sessions, and the efficacy of both treatments was maintained. This case broadens the drug's clinical applications and it helps in choosing the appropriate medical regimen in patients requiring both treatments.