Successful management of a Jehovah's Witness with thrombotic thrombocytopenic purpura unwilling to be treated with therapeutic plasma exchange

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease treated successfully with plasma exchange. Jehovah's Witnesses whose religious beliefs preclude them from accepting plasma exchange may require alternative forms of therapy. We report a case of one such patient who presented with TTP, whom we successfully managed with vincristine and responded favorably without the need for plasma exchange.     

Survival of a Jehovah's Witness with thrombotic thrombocytopenic purpura without using plasma: A case report and review of the literature

Acquired thrombotic thrombocytopenic purpura (aTTP) is a serious disorder with arteriolar and capillary thrombosis for which the treatment usually requires plasma exchange with plasma as the replacement fluid. Management of patients who do not accept blood products is a serious challenge. We present the case of a Jehovah's Witness patient who achieved clinical response after treatment with plasma exchange using human albumin solution as the replacing fluid, high dose corticosteroids, and rituximab. The patient also received ADAMTS13 containing plasma cryoprecipitate and von Willebrand factor VIII concentrates. She had an exacerbation of her TTP in less than 3 weeks. She was treated with further plasma exchange with human albumin solution as the replacement fluid, high dose steroids, and rituximab. Bortezomib and N-acetylcysteine were added. The patient eventually improved clinically and achieved remission that is ongoing for more than 7 months. A review of the literature shows that all five previously reported cases of aTTP in Jehovah's Witnesses survived although none received plasma. Two were not even treated with plasma exchange. The experience of this case and those in the literature demonstrates that remission of aTTP may be achieved without using plasma or plasma exchange.     

Successful repeat therapy with rituximab for relapsed thrombotic thrombocytopenic purpura

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease that is treated successfully with therapeutic plasma exchange (TPE) and often with corticosteroids; however, almost one third of TTP patients have treatment failures that require either long-term TPEs or other adjunct therapies. Recent insights into the autoimmune-pathophysiology of this disease provide the rationale for immune-based therapies. Cumulative evidence suggests that rituximab, an anti-CD20 antibody that depletes B-cells temporarily, is an effective therapy in patients with refractory or relapsing TTP. We report here two patients with chronic relapsing TTP who were treated successfully with rituximab. However, both experienced TTP relapse following sustained and prolonged remissions for 21 and 37 months, respectively. They responded favorably with repeat therapy with rituximab. The benefits of rituximab treatment for refractory or relapsing TTP as well as in the prevention of recurrences are discussed.     

A systematic review of randomized controlled trials for plasma exchange in the treatment of thrombotic thrombocytopenic purpura

The mainstay of treatment for thrombotic thrombocytopenic purpura (TTP) is plasma exchange (PE). A systematic review was undertaken to summarize the randomized controlled trial (RCT) evidence, to date, on PE as treatment for TTP. Seven randomized RCTs were identified till May 2005. A statistical reduction in mortality was found in patients receiving PE compared with patients receiving plasma infusion (relative risk 0.31, 95% confidence interval 0.12-0.79). No statistical difference in mortality was found in trials comparing different replacement fluids for PE. There were few differences in the response to treatment and the resolution of the presenting signs of TTP in any trial. Lack of data prevented a full assessment of the incidence of adverse events. None of the studies included measured patients' quality of life. Further research is required to determine the benefits and side effects associated with different replacement fluids for PE. It is recommended that there should be consistency in the diagnostic criteria, measurement of clinical outcomes and length of follow up. Continued support of existing TTP patient registries and establishment of new registries would facilitate this.     

Treatment of thrombotic thrombocytopenic purpura with plasma exchange: Five cases

Five patients with thrombotic thrombocytopenic purpura (TTP) were treated with corticosteroids, plasma exchange (PE), and antiplatelet agents. ABO- and Rh-compatible fresh-frozen plasma (FFP) was used as the replacement fluid. None of the patients received FFP infusion without PE. The patients were followed for 14–32 months after initial treatment. Four of the five patients are in complete clinical remission. One responded to plasma exchange but died of heart disease. This report shows an 80% survival rate which is markedly better than that without the use of PE and FFP infusion. We found dramatic clinical and hematologic improvement beginning shortly after initiating treatment. Two patients showed reversal of their initial clinical and hematologic improvement when PE was discontinued, despite continuing treatment with antiplatelet drugs and in one with corticosteroids. Both patients showed hematologic and clinical remission after reinstitution of PE. None of the survivors had any neurologic or renal deficit. They were maintained on aspirin and dipyridamole for 1 year after discharge.     

血浆置换治疗血栓性血小板减少性紫癜及影响因素研究

目的 探讨血浆置换(PE)治疗血栓性血小板减少性紫癜(TTP)临床疗效评价及影响因素的相关性研究.方法 对12例TTP患者进行PE治疗,每例连续进行3次以上,每次置换60～80 ml/kg,治疗期间同时运用免疫抑制剂.结果 12例TTP患者中,2例死亡,1例转院,9例患者贫血纠正,出血症状好转,发热消退,血小板计数上升至正常水平,肾功能(肌肝、尿素氮)指标恢复正常,乳酸脱氢酶(LDH)下降至400 U/L以下,6例痊愈出院,3例临床症状得到缓解和控制,有效率达75%.结论 PE治疗对TTP患者疗效显著,禁忌输注血小板与冷沉淀.     

First two patients with ulcerative colitis who developed classical thrombotic thrombocytopenic purpura successfully treated with medical therapy and plasma exchange

The association of ulcerative colitis (UC) and thrombotic thrombocytopenic purpura (TTP) is rare. Only one prior patient with these two syndromes has been reported in the literature. In that case, splenectomy and proctectomy were performed to control the symptoms of TTP. We present two patients with UC who developed TTP and were successfully treated with multiple plasma exchanges (PEXs) in conjunction with medical therapy without the necessity for surgical intervention. Acquired TTP may be another extraintestinal autoimmune feature of UC. TTP in association with UC may be refractory to high-dose steroids and PEX, possibly requiring vincristine and splenectomy, as in the one previously reported case, to achieve remission.     

Treatment of thrombotic thrombocytopenic purpura with plasma exchange,antiplatelet agents,corticosteroid, and plasma infusion: Mayo clinic experience

Ten patients with thrombocytopenia (TTP) were treated recently in our institution with plasma exchange (PE), steroids, and antiplatelet drugs. Additionally, fresh frozen plasma (FFP) was administered to nine patients, with folic acid given to eight patients. After 13 to 25 months of follow-up, we found that four patients achieved and remained in remission after initial treatment. Three patients had four relapses, which developed while they were taking antiplatelet therapy, and which were treated successfully with FFP alone, or with PE in addition to FFP. Four patients suffered major neurological or renal damage during their presentation or initial treatment. One of these patients died during his initial hospitalization. Another patient died 7 months after initial treatment. After analyzing this experience, we have concluded that antiplatelet drugs or corticosteroid should be used as the sole initial treatment most cautiously. The relative importance of the exchange process, per se, versus plasma infusion cannot be inferred from our observations, but plasma exchange with FFP appears to have had a real impact on recovery.     

Questionable efficacy of plasma exchange for thrombotic thrombocytopenic purpura after bone marrow transplantation

Thrombotic thrombocytopenic purpura (TTP) after bone marrow transplantation (BMT) is an uncommon complication presumably associated with extensive endothelial cell damage due to Cyclosporine, total body irradiation, or other drugs. While the majority of patients with primary TTP, which is considered to be an autoimmune process, respond to plasma exchange, TTP after BMT has a very poor prognosis. A total of 7 patients out of 307 patients who underwent BMT were diagnosed with TTP during 1989-1999. The diagnosis of TTP was made based on thrombocytopenia and microhemangiopathic hemolytic anemia characterized by an elevated LDH and the presence of schistocytes on the peripheral blood smear. Five patients were treated with plasma exchange (PE) using fresh frozen plasma and/or cryoprecipitate poor plasma as replacement fluid. One patient was treated using a protein A column. One patient did not receive plasma exchange because the 125 patient was clinically stable and was discharged. It was hard to assess the efficacy of PE due to the multiplicity of the patients' clinical condition and laboratory data. At least 4 patients did not respond to PE and 2 patients were not able to be evaluated due to multi organ failure. However, all patients died. It is not clear at this moment if PE for patients with TTP after BMT is truly beneficial.     

Unilateral serous retinal detachment in a patient with thrombotic thrombocytopenic purpura

Ocular complications are a relatively common occurrence in patients with thrombotic thrombocytopenic purpura (TTP). Serous retinal detachment is a rare but reported complication, with most cases being bilateral and associated with concomitant hypertension. Therapeutic plasma exchange has been used to successfully treat patients with TTP. We report a case of a 46 year old woman who presented with TTP, received therapeutic plasma exchange, and developed unilateral serous retinal detachment with retinal pigment epithelial tear in the absence of reported hypertension. The increased perfusion pressure due to hypertension, combined with the choroidal vasculature damage from TTP are thought to lead to retinal epithelial tear. This suggests that although hypertension may play a role in retinal detachment in these patients, other mechanisms may be responsible.     

Deterioration of gas exchange in patients with severe thrombotic thrombocytopenic purpura with respiratory failure during therapeutic plasma exchange

Therapeutic plasma exchange (TPE) is a procedure performed on patients suffering from various disorders, including thrombotic thrombocytopenic purpura (TTP). As we noted a frequent transient deterioration in respiratory function when the procedure was performed on intensive care unit (ICU) patients, we studied retrospectively the incidence of respiratory deterioration during and shortly after TPE and looked for a probable correlation with a change in the white blood cell (WBC) counts. Over a period of 10 months six patients with TTP, five of whom had parenchymal lung disease due to different medical reasons, underwent TPE. The oxygen saturation was measured continuously before, during, and after TPE; additionally, the WBC and differential counts were measured pre‐ and post‐TPE. The ratio of the oxygen saturation by pulse oxymetry (SpO₂) to the fraction of inspired oxygen (FiO₂) was calculated before, during and after TPE. In these five patients with lung disorders, there was a consistent trend of a decreasing SpO₂/FiO₂ quotient during and within 2 h post TPE compared to the pre‐TPE value. The decrease in SpO₂/FiO₂ range was 0.20–0.89 with an average of 0.56. In the same 5 patients there was an increase in the WBC count in the range of 2.3–19.7 × 10⁹/L with an average increase of 9.3 × 10⁹/L. The percent neutrophils of the total WBC counts also increased following most of the sessions, this increase was in the range of 1–15 % with an average of 7%. The effect of TPE on the SpO₂/FiO₂ ratio and the correlation to the WBC count and to a possible neutrophil activation has not been previously reported. We postulate that TPE can accentuate respiratory deterioration in patients with TTP who already have acute lung injury. This may be due to the priming and activation of the leukocytes that could lead to the release of cytokines and inflammatory mediators during the procedure. Thus, it is important to be aware of the possible deterioration in respiratory function and gas exchange while administering TPE to patients with pre‐existing parenchymal lung injury. J. Clin. Apheresis. 16:143‐147, 2000. © 2001 Wiley‐Liss, Inc.     

1例重症新型布尼亚病毒患者继发血栓性血小板减少性紫癜的护理

新型布尼亚病毒又称发热伴血小板减少综合征布尼亚病毒(severe fever with thrombocytopenia syndrome bunyavirus,SFTSV),是以发热伴血小板减 少为主要特征的新型传染性疾病,临床表现主要为发热、血小板减少、白细胞减少及多器官功能损害[1].     

Rituximab as an adjunct to plasma exchange in TTP: a report of 12 cases and review of literature

Idiopathic thrombotic thrombocytopenic purpura (TTP) is caused by the production of autoantibodies against the Von Willebrand factor cleaving enzyme. This provides a rationale for the use of rituximab in this disease. We report a retrospective review of 12 patients treated with rituximab for TTP refractory to plasma exchange. Eleven patients were treated during initial presentation, and one patient was treated for recurrent relapse. Ten patients responded to treatment. Median time to response after first dose of rituximab was 10 days (5-32). Of the 11 patients treated during initial presentation, nine remain free of relapse after a median follow-up of 57+ months (1+-79+). Two patients died during initial treatment. One patient was lost to follow-up 1 month after achieving complete response. The patient treated for recurrent disease during second relapse remained disease free for 2years, relapsed and was treated again with rituximab, and was in remission for 22 months. She relapsed again, was retreated, and has now been in remission for 21+ months. We conclude that rituximab is an useful addition to plasma exchange treatment in TTP, but its exact role and dosing need to be verified in prospective studies.     

A case series of atypical presentations of thrombotic thrombocytopenic purpura

Thrombotic thrombocytopenic purpura (TTP) is a heterogeneous disease primarily characterized by thrombocytopenia and microangiopathic hemolytic anemia. Therapeutic plasma exchange has dramatically improved mortality, allowing for emergence of refractory, relapsing, and atypical presentations. In this article, we describe four cases of TTP presenting with minimal schistocytes, mild elevation of lactate dehydrogenase, and symptoms suggestive of macrovascular arterial involvement. With increasing reports of less common presentations of TTP, clinicians should consider this diagnosis in cases of unexplained arterial thrombosis, thrombocytopenia, or hemolytic anemia. Testing for a disintegrin and metalloprotease with thrombospondin Type 1 motif, Member 13 ADAMTS13 activity was extremely useful to help confirm the diagnosis in our series of patients.     

Treatment of thrombotic thrombocytopenic purpura: A role for early vincristine administration

Plasma exchange (PE) is considered first-line treatment for thrombotic thrombocytopenic purpura (TTP) to the point that many clinicians regard it as definitive therapy. Studies have reported response rates to PE ranging from 39% to 78%. In our experience, a minority of patients have been cured solely by PE. While adjuvant therapies (e.g., vincristine, splenectomy) have proved effective in anecdotal reports, protocols using these therapies in the treatment of TTP have not been established. Management of TTP over a 15-year period was reviewed to evaluate (1) the rate of cure accomplished by PE alone, and (2) the potential benefit of additional therapies. The records of 29 consecutive patients with TTP treated by PE were reviewed and classified according to response to PE alone and the need for adjuvant therapy. Eight patients (28%) achieved remission and long-term survival with PE alone. With the addition of adjuvant therapy another 13 patients survived, bringing the total survival to 72%. Fifteen patients were treated with vincristine in addition to PE. Only three of seven patients receiving vincristine after failing to respond completely to PE survived, but survival increased to 88% (7 of 8) when vincristine was administered within 3 days of beginning PE. These data suggest that PE alone may not be sufficient therapy for most patients with TTP. Additional therapy is often needed to achieve long-term survival. While controlled trials will be necessary to prove the efficacy of vincristine, we believe that, given the minimal risk of vincristine toxicity and the grave consequences of ineffective therapy, routine administration of vincristine early in the course of PE should be considered. J. Clin. Apheresis 13:20–22, 1998. © 1998 Wiley-Liss, Inc.     

血浆置换联合激素、免疫抑制剂治疗血栓性血小板减少性紫癜13例的护理

目的探讨血浆置换(PE)联合激素、免疫抑制剂治疗血栓性血小板减少性紫癜(TTP)的护理方法。方法对13例行血浆置换联合激素、免疫抑制剂治疗的TTP患者,给予心理护理,做好血浆置换、激素及免疫抑制剂应用的观察及护理,出院指导。结果本组13例患者中,3例因各种原因未坚持治疗自动出院,其余10例均缓解出院。结论及时有效的治疗,严密的病情观察,全面细致的护理,预防和减少并发症,是TTP患者康复的重要保证。