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.     

Staphylococcus aureus bacteremia as a cause of early relapse of thrombotic thrombocytopenic purpura

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a multisystem disease characterized by the sudden onset of hemolytic anemia, thrombocytopenia, fever, renal failure, and neurologic dysfunction, occurring in various combinations. The most effective treatment of TTP is plasma exchange and the administration of corticosteroids, which reduces mortality from the 90 percent seen in untreated patients to 10 percent. CASE REPORTS: Two patients responded favorably to plasma exchange and corticosteroid therapy, but their TTP relapsed during treatment. In both cases, the early relapse of TTP was associated with Staphylococcus aureus bacteremia secondary to central line infection. Treatment of the infection and intensification of the plasma exchange regimen resulted in a sustained remission. CONCLUSION: Infection should be actively sought and treated in TTP patients who are refractory to treatment or in whom an exacerbation of the disease occurs while they are undergoing plasma exchange.     

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.     

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.     

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.     

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.     

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].     

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.     

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.     

Relapsed thrombotic thrombocytopenic purpura presenting as an acute cerebrovascular accident

Thrombotic thrombocytopenic purpura (TTP) is an uncommon but severe disorder that classically presents with microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and fluctuating neurological changes. Previously, it was impossible to make a diagnosis of TTP in the absence of thrombocytopenia or microangiopathic hemolysis (MAHA). We describe two cases of relapsing TTP that presented with acute cerebrovascular accident (CVA) without concurrent thrombocytopenia or MAHA after initial classical presentation of TTP. In both cases, the diagnosis of TTP as the cause of the CVA was attributed to severe deficiency of the von Willebrand factor cleaving protease, ADAMTS13 in plasma (11 and 12%, normal 79-127%). Each patient had a dramatic clinical improvement in response to therapeutic plasma exchange. The experience in these two cases suggests that TTP should be considered as a potential cause among patients presenting with a CVA, particularly if the patients have a history of TTP.     

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：     

External validation of the PLASMIC score: a clinical prediction tool for thrombotic thrombocytopenic purpura diagnosis and treatment

Essentials

• Severe ADAMTS‐13 deficiency is key to thrombotic thrombocytopenic purpura (TTP) diagnosis.
• PLASMIC score predicts ADAMTS‐13 deficiency in suspected TTP with high discrimination.
• PLASMIC score is more generalizable with fewer missing data than alternative clinical scores.
• PLASMIC score identifies a subgroup of patients lacking significant response to plasma exchange.

Summary

Background

The PLASMIC score was recently published to distinguish patients with severe ADAMTS‐13 deficiency from those without for early identification of thrombotic thrombocytopenia purpura (TTP).

Objective

We performed an independent external validation of the PLASMIC score for clinical prediction of severe ADAMTS‐13 deficiency.

Patients/Methods

We studied an independent cohort of 112 consecutive hospitalized patients with suspected thrombotic microangiopathy and appropriate ADAMTS‐13 testing (including 21 patients with TTP diagnosis).

Results

The PLASMIC score model predicted severe ADAMTS‐13 deficiency with a c statistic of 0.94 (0.88–0.98). When dichotomized at high (score 6–7) vs. low‐intermediate risk (score 0–5), the model predicted severe ADAMTS‐13 deficiency with positive predictive value of 72%, negative predictive value of 98%, sensitivity of 90% and specificity of 92%. In the low‐intermediate risk group (score 0–5) there was no significant improvement in overall survival associated with plasma exchange.

Conclusions

The PLASMIC score model had excellent applicability, discrimination and calibration for predicting severe ADAMTS‐13 deficiency. The clinical algorithm allowed identification of a subgroup of patients who lacked a significant response to empiric treatment.     

Thrombotic thrombocytopenic purpura: Evolution across 15 years

Thrombotic thrombocytopenic purpura (TTP) was originally described 70 years ago. It is considered an uncommon disorder with a reported occurrence rate of one case per 1 million patients. Mortality has decreased from almost 100% early on to 30–50% with the advent of newer treatment methods. We reviewed 41 patients with a diagnosis of TTP spanning the years 1980 to mid 1994. We found a much higher case rate, one per 6000 hosptial admissions, and an overall death rate of 40%. However, isolating 5 year periods we noted a marked fall in mortality from 54% (1980–1984), 44% (1985–1989), to 18% (1990–1994). Previous reports describe relapsing TTP and report an incidence of 7–15% although very recent data suggests a higher incidence. In our study, we found an overall relapse rate of 25% and by 5 year periods 23% (1980–1984), 13% (1985–1989), and 46% (1990–1994). We suggest that the improvement in survival and the increase in relapse rate are related and reflect more effective therapy for this once almost always fatal disease. Patients now survive their initial episode and thus are at risk for recurrence. Identification of risk factors for relapse will require further study. © 1996 Wiley-Liss, Inc.     

Acute thrombotic thrombocytopenic purpura and cholecystitis

Acute thrombotic thrombocytopenic purpura (TTP) is a rare, usually fatal, disease characterized by widespread deposition of microvascular occlusive thrombi of platelets and fibrin. Although its exact etiology is unknown, numerous case reports in the medical literature have linked TTP with a variety of medical conditions, including systemic infections, vaccinations, pregnancy, and autoimmune diseases. A case of acute TTP occurring in a 28-year-old white male is presented and discussed, with emphasis on emergency department diagnosis and management. This patient's treatment included splenectomy. When laparotomy was performed for this procedure, the patient was found to have a distended, inflamed gallbladder, and a cholecystectomy was also performed. A review of the medical literature reveals this to be the first reported case of TTP occurring in association with cholecystitis.     

Successful management of thrombotic thrombocytopenic purpura in a Jehovah's Witness without plasma exchange

Thrombotic thrombocytopenic purpura (TTP) is a hematologic emergency characterized by microangiopathic hemolytic anemia and thrombocytopenia. Plasma exchange is the standard treatment. Treating TTP without plasma exchange is a challenge. Due to religious beliefs, Jehovah's Witnesses do not accept transfusions of blood products. We report a case of successful treatment of TTP in a Jehovah's Witness using plasma exchange with albumin replacement. J. Clin. Apheresis 30:46–49, 2015. © 2014 Wiley Periodicals, Inc.     

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.     

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。     

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.