血栓性血小板减少性紫癜18例临床分析

目的:了解血栓性血小板减少性紫癜(TTP)的临床特征及治疗,以加深对该病的认识。方法:对我院1998年6月～2005年10月诊断的18例TTP的类型、临床表现、治疗及预后进行回顾性分析。结果:患者多为女性;临床主要表现TTP、微血管性溶血性贫血和神经系统症状;血小板计数和血红蛋白减低;血清乳酸脱氢酶明显升高;凝血功能基本正常;血浆置换和免疫抑制治疗有效;复发率40%,再次治疗有效。结论:TTP是一种女性多见的微血管血栓-出血综合征,血管性血友病因子裂解蛋白酶(ADAMTS13)活性降低参与了TTP的发生,应根据TTP的类型选择不同的治疗方案以提高疗效、减少复发。     

Systemic lupus erythematosus and thrombotic thrombocytopenic purpura: a case report and literature review

We describe a patient with systemic lupus erythematosus (SLE) who developed severe and acute thrombotic thrombocytopenic purpura (TTP). Detection of the fragmentation of peripheral red blood cells (RBC) helped the early diagnosis of TTP and the patient was rescued by extensive plasma exchange started promptly after the diagnosis. Because manifestations of TTP are similar to those in SLE, it is sometimes difficult to make an accurate diagnosis of TTP in SLE patients. We emphasise here the significance of the early diagnosis of TTP by the observation of fragmented RBC and the intensive therapy, including plasma exchange, for this very severe condition.     

Therapeutic plasma exchange in patients with grade 2-3 hematopoietic stem cell transplantation-associated thrombotic thrombocytopenic purpura: a ten-year experience

In the present retrospective study we report our 10-year experience with therapeutic plasma exchange (TPE) in 18 patients with grade 2-3 hematopoietic stem cell transplantation (HSCT)-associated thrombotic thrombocytopenic purpura (TTP). During TPE a mean total quantity of 26.5 +/- 15.1 L of plasma was exchanged. Five patients (27.7%) had a complete response eight patients (44.4%) had a partial response while five patients (27.7%) died during TPE treatment. Among the survivors, relapse of TTP occured in three patients (23%) and although these patients were treated again with TPE, all died. First-year survival rate was 41.2%. Our results indicate that TPE may be effective in the treatment of some patients with grade 2-3 HSCT-associated TTP.     

Successful treatment of thrombotic thrombocytopenic purpura with repeated plasma exchange in a patient with microscopic polyangitis

Thrombotic thrombocytopenic purpura (TTP) is in rare cases associated with antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis, and often has a fatal outcome. We report the case of a 77-year-old woman with microscopic polyangitis (MPA) presenting with TTP. Rapidly progressive renal dysfunction and paralysis and sensory disturbance of the left lower limb were noted. Serum creatinine was 3.95 mg/dl, and the titer of myeloperoxidase-ANCA was 238 EU. She was diagnosed with MPA, and high-dose methylprednisolone was initiated, followed by 60 mg/day of prednisolone. Hemolytic anemia with red blood cell fragmentation, purpura, and thrombocytopenia developed during the course of active MPA. The activity of disintegrin and metalloproteinase with thrombospondin type 1 motifs 13 (ADAMTS13) was moderately decreased (27%). She was diagnosed with TTP, and plasma infusion was initiated, followed by plasma exchange (PE) with 40 units of fresh frozen plasma. Thrombocytopenia continued for more than a month (5–10 × 10⁴/μl). PE was repeatedly performed two or three times a week during the first 8 weeks from the beginning of PE in addition to prednisolone. Her clinical and laboratory findings gradually improved, and ADAMTS13 activity increased to 68%. The findings in this case suggested that ANCA-associated vasculitis may be involved in the development and the pathogenesis of TTP, and that repeated PE may need to be performed in addition to immunosuppressive therapy.     

Successful treatment of thrombotic thrombocytopenic purpura with repeated plasma exchange in a patient with microscopic polyangitis

Abstract

Thrombotic thrombocytopenic purpura (TTP) is in rare cases associated with antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis, and often has a fatal outcome. We report the case of a 77-year-old woman with microscopic polyangitis (MPA) presenting with TTP. Rapidly progressive renal dysfunction and paralysis and sensory disturbance of the left lower limb were noted. Serum creatinine was 3.95 mg/dl, and the titer of myeloperoxidase-ANCA was 238 EU. She was diagnosed with MPA, and high-dose methylprednisolone was initiated, followed by 60 mg/day of prednisolone. Hemolytic anemia with red blood cell fragmentation, purpura, and thrombocytopenia developed during the course of active MPA. The activity of disintegrin and metalloproteinase with thrombospondin type 1 motifs 13 (ADAMTS13) was moderately decreased (27%). She was diagnosed with TTP, and plasma infusion was initiated, followed by plasma exchange (PE) with 40 units of fresh frozen plasma. Thrombocytopenia continued for more than a month (5–10 × 10⁴/μl). PE was repeatedly performed two or three times a week during the first 8 weeks from the beginning of PE in addition to prednisolone. Her clinical and laboratory findings gradually improved, and ADAMTS13 activity increased to 68%. The findings in this case suggested that ANCA-associated vasculitis may be involved in the development and the pathogenesis of TTP, and that repeated PE may need to be performed in addition to immunosuppressive therapy.     

A case report of uncompensated alkalosis induced by daily plasmapheresis in a patient with thrombotic thrombocytopenic purpura

Plasmapheresis (PP) is widely known as the standard therapy for thrombotic thrombocytopenic purpura (TTP). Citrate is used as an anticoagulant in fresh frozen plasma, and the large amount of citrate infused during PP induces metabolic alkalosis. A 29-year-old woman was diagnosed with TTP associated with systemic lupus erythematosus, and was treated by daily PP in addition to a steroid, an immunosuppressant, vincristine, and cyclophosphamide. Uncompensated alkalosis caused by a combination of metabolic and respiratory alkalosis developed after artificial ventilation was discontinued. Her metabolic status improved after controlling her respiratory status and the activity of the TTP. Metabolic alkalosis is a common complication in TTP patients treated by frequent PP, but several factors that affect metabolic status may aggravate the alkalosis and induce uncompensated alkalosis.     

血栓性血小板减少性紫癜8例临床分析

目的：探讨血栓性血小板减少性紫癜（TTP）的临床特点和疗效。方法：1996年以前,5／8例应用泼尼松,肝素,双嘧达莫等治疗,仅1例缓解,4例死亡,1997年后,3／8例采用血浆置换（PE）加泼尼松,肝素,双嘧达莫等治疗,3例缓解,结果：随访1－3年,2例健康,1例复发,死于肾功能衰竭。结论：TTP为多系统损伤的严重疾病,PE是TTP的首选治疗。     

Late response to cyclosporine in refractory thrombotic thrombocytopenic purpura

Plasma exchange (PEX) with fresh frozen plasma, usually in association with steroid therapy, has been shown to be the first-line treatment of thrombotic thrombocytopenic purpura. It works by removing ultralarge von Willebrand factor (vWF) multimers and inhibitory antibody and by supplying normal protease. For patients with disease refractory to PEX, there is no standardized treatment. Limited and sporadic success with different therapies (vincristine sulfate, prostacyclin, intravenous immunoglobulins, splenectomy) has been described. We report the case of a woman who developed refractory disease after an initial response to PEX and despite a very high number of PEX procedures performed. Low activity (< 5%) of serum vWF-cleaving protease and a low level of protease inhibitor were documented. The patient had a slow but sustained response when oral cyclosporine was administered concomitantly with PEX, which was slowly tapered. The activity of serum vWF-cleaving protease normalized. At relapse, treatment with cyclosporine, added after the failure of steroids and PEX, led to a lasting response. It is possible that in some cases cyclosporine therapy must be of particularly long duration before being considered ineffective.     

Retrospective Review of 25 Cases of Thrombotic Thrombocytopenic Purpura in Pakistan

Thrombotic thrombocytopenic purpura (TTP) is a disorder characterized by thrombocytopenia, microangiopathic hemolytic anemia, fever, neurological abnormalities, and renal dysfunction. Because of the rarity of TTP, no comprehensive data is available in the Pakistani population. The present study aimed to review the therapeutic interventions, relapses and mortality rate in patients with TTP treated at a tertiary care hospital in Pakistan. This was a retrospective review of patients treated over a period of more than nine years (2001–2010). Medical charts were retrieved using the ICD coding system version 9 and each file was reviewed by the principal author for clinical and laboratory details, along with the therapy utilized and the outcome. Twenty‐five patients were diagnosed with TTP, including nine males (36%) and 16 females (64%) with a median age of 30 ± 18.4 years for all patients. Idiopathic TTP was seen in 17 patients (68%) and secondary causes were identified in eight (32%). Patients were treated with plasma exchange once the diagnosis of TTP was established. Only neurological and renal involvement at the time of presentation emerged as important indicators in determining the outcome and response to treatment. Most of our patients tolerated plasmapheresis very well; however, delay in starting plasmapheresis due to late presentation was a major hurdle in our set up.     

Rituximab in the treatment of relapsed thrombotic thrombocytopenic purpura

Several reports have defined nonfamilial thrombotic thrombocytopenic purpura (TTP) as an autoimmune disorder caused by antibodies to von Willebrands factor-cleaving protease (vWF-CP). This raises the possibility that rituximab, a monoclonal antibody against CD20 present in B-lymphoid cells, may have utility in the treatment of TTP. We report five consecutively treated patients with relapsed TTP who responded rapidly to immune suppression by rituximab at our institution. These two male and three female patients had a median age of 37 years (27–70). The median time from diagnosis to therapy was 24 months (8–60). Prior therapies included plasma exchange and corticosteroids in all cases, splenectomy (4), vincristine and aspirin (3), and azathioprine (2). The median number of plasma exchanges received prior to therapy was 59 (21–158). The cohort had a median platelet count of 48×10⁹/l (23–110), median hemoglobin of 9 g/dl (8–11), and median lactate dehydrogenase of 632 IU/l (311–945) prior to administration of rituximab. Analysis of vWF-CP activity demonstrated absent or decreased activity with detectable inhibitors in four patients. All patients attained a complete response. The median time to response after the first dose of rituximab was 5 weeks. Responses are maintained in all patients from 10 to 21 months after treatment. This report adds to the evidence that rituximab has efficacy in nonfamilial TTP and warrants further study.     

Anti-CD20 antibody in thrombotic thrombocytopenic purpura refractory to plasma exchange

Thrombotic thrombocytopenic purpura is a rare condition characterized by microangiopathic haemolytic anaemia, thrombocytopenia, altered neurology, renal impairment and fever. While plasma exchange has reduced mortality from more than 90% to between 10 and 30%, a proportion of cases fail to respond. Rituximab may be efficacious in the management of refractory cases of thrombotic thrombocytopenic purpura. We present two cases in which rituximab was used with successful outcomes. Treatment resulted in resolution of severe clinical and haematological abnormalities in both patients. There has been no relapse after 16 months follow up. Our experience supports the use of rituximab in difficult cases of TTP. Ongoing evaluation of its use is in progress at our institution.     

A case report of total abdominal hysterectomy resulting in acute thrombotic thrombocytopenic purpura with pancreatitis and hepatitis: complete resolution with plasma exchange therapy

Acute thrombotic thrombocytopenic purpura (TTP) is a life-threatening disorder that has previously been described associated with various types of surgery. An association between total abdominal hysterectomy (TAH) and TTP has never been reported. Thrombotic thrombocytopenic purpura is classically characterized by thrombocytopenia, microangiopathic hemolytic anemia, fever, azotemia and neurological manifestations. Atypical manifestations of TTP include hepatitis, pancreatitis, acute respiratory distress syndrome, non-occlusive mesenteric ischemia and peripheral digital ischemia. This case report describes the occurrence of acute TTP following TAH and bilateral salpingo-oopherectomy, which manifested with typical and atypical features (i.e. hepatitis, pancreatitis). Plasma exchange therapy resulted in the complete resolution of the process.     

Citrate anticoagulation during plasma exchange in a patient with thrombotic thrombocytopenic purpura: short heparin-free hemodialysis helps to attenuate citrate load

The treatment of thrombotic thrombocytopenic purpura requires plasma exchange using fresh frozen plasma as a replacement solution once or even twice daily. If citrate anticoagulation is needed, the citrate load (both from fresh frozen plasma and citrate as an anticoagulant) can be significant, causing metabolic complications. The aim of our report is to present our experience with citrate anticoagulation in a patient with thrombotic thrombocytopenic purpura treated with daily membrane plasma exchange. Twenty-six plasma exchange procedures were performed during 20 days of treatment in a 46-year-old female. The blood flow was 98 +/- 8 mL/min; 4% trisodium citrate was infused into the arterial line (134 +/- 11 mL/h) and 1 M CaCl2 into the venous line (11.4 +/- 1.8 mL/h). Fresh frozen plasma (first 7 procedures) or cryo-poor plasma (19 procedures) were used as a replacement solution, 3176 +/- 536 mL per procedure. A total of 88,930 mL of plasma was exchanged. No serious side-effects occurred. iCa before plasma exchange was significantly higher than afterwards (1.23 +/- 0.12 vs. 1.12 +/- 0.12, P = 0.0047). Significant alkalosis occurred after three plasma exchanges (pH 7.64, bicarbonate 36.2 mmol/L), and was corrected by 3-h heparin-free hemodialysis with dialysate as follows: K 4.0 mmol/L, calcium 1.5 mmol/L, and bicarbonate set to 24 mmol/L. After dialysis, pH was 7.45 and bicarbonate 29.4 mmol/L. Another (2-h) heparin-free hemodialysis procedure was repeated after six plasma exchanges. Citrate anticoagulation can be safely performed in patients treated with plasma exchange once or twice daily. Periodically performed short heparin-free hemodialysis can correct metabolic alkalosis and attenuate the citrate load.     

Early relapse of thrombotic thrombocytopenic purpura during therapeutic plasma exchange associated with Acinetobacter anitratus bacteremia

Thrombotic thrombocytopenic purpura (TTP)/Hemolytic-uremic syndrome (HUS) is a syndrome characterized by thrombocytopenia, microangiopathic hemolytic anemia, fever, renal failure and neurologic manifestation. Almost all cases are idiopathic. However, secondary TTP/HUS associated with viral, bacterial and mycobacterial infections, drugs, connective tissue disease, solid tumors, bone marrow transplantation and pregnancy have been described. Early relapse associated with infection is a rare occurrence. The patient we report had a classic case of postdiarrheal TTP/HUS that responded to plasmapheresis but relapsed during treatment as reflected by the increased schistocytosis, decreased hematocrit, increased lactate dehydrogenase, and decreased platelet counts. This relapse may be attributed to Acinetobacter anitratus bacteremia, secondary to central line infection. Administration of antimicrobial treatment resulted initially in a mild improvement. However, this was followed by a fatal relapse. The importance of monitoring the possible bacterial colonization of an indwelling catheter is thus emphasized.     

Fatal thrombotic thrombocytopenic purpura as a rare complication following allogeneic stem cell transplantation

 Thrombotic thrombocytopenic purpura (TTP) is a rare disease which, together with hemolytic uremic syndrome, is subsumed under thrombotic microangiopathy. After stem cell transplantation (SCT), this syndrome represents a possibly fatal complication with a higher incidence in allogeneic SCT than in autologous SCT. Although plasmapheresis offers an encouraging treatment modality in classic TTP, this seems less effective in bone marrow transplant-associated microangiopathy. This is probably due to a different etiology. We present a case of transplant-associated TTP with a fatal outcome despite multiple courses of plasmapheresis. Received: 11 November 1999 / Accepted: 23 February 2000     

Atypical presentations of thrombotic thrombocytopenic purpura

Thrombotic thrombocytopenic purpura (TTP) usually presents in a fulminant fashion with marked hematologic abnormalities often associated with fever and neurologic and renal abnormalities. Two cases of TTP are reported in which neurologic deficits were initially the dominant findings, followed weeks later by the pronounced hematologic manifestations. Young patients with unexplained neurologic findings, even if there is only minimal anemia or thrombocytopenia, should be monitored for subsequent manifestations of TTP so that treatment may be instituted promptly.     

Rituximab in a child with autoimmune thrombotic thrombocytopenic purpura refractory to plasma exchange

A nine-year-old girl presented with headache, purpura and mild left hemiparesis. Laboratory evaluation revealed thrombotic microangiopathy with ADAMTS13 deficiency, with auto-antibodies to ADAMTS13. She was treated with plasma exchange and steroids, following which she improved transiently, relapsing within 2?months. The relapse was refractory to conventional therapy and rituximab was tried. She had good response to rituximab and has been in remission for the past 12?months. Rituximab may be a promising option for children with acquired TTP refractory to plasma exchange and steroids.     

A case of thrombotic thrombocytopenic purpura in an adult treated with vincristine

 The case of a woman with thrombotic thrombocytopenic purpura refractory to prolonged treatment with plasma exchange and steroid treatment is described. The addition of vincristine yielded a complete response, which has been maintained for 9 months up to the time of this report. Received: May 29, 1998 / Accepted: September 11, 1998     

Life-threatening thrombotic thrombocytopenic purpura (TTP) in a patient with sickle cell-hemoglobin C disease

We report a patient with hemoglobin sickle cell-hemoglobin C disease who developed the clinical syndrome of thrombotic thrombocytopenic purpura (TTP) during admission for typical acute pain crisis. The potential for multiorgan involvement secondary to vaso-occlusive crisis complicated the diagnosis and overlapped with the patient's clinical presentation of chronic bone pain and hemolytic anemia. Clinical improvement and normalization of laboratory parameters followed rapidly in response to plasma exchange therapy.