Idiopathic thrombocytopenic purpura during remission of thrombotic thrombocytopenic purpura

Three patients were treated empirically with anti-platelet agents, prednisone, plasmapheresis, and prostacyclin for the classical clinical syndrome of thrombotic thrombocytopenic purpura (TTP). All three patients initially responded, then relapsed after one to 13 months with a clinical picture characteristic of immunogenic thrombocytopenic purpura (ITP). At relapse, all three had thrombocytopenia without microangiopathy or other causes of thrombocytopenia. All responded to splenectomy. This complication of TTP may become more common with improved survival in TTP. Recognition may prevent inappropriate therapy.     

Diagnosis of thrombotic thrombocytopenic purpura

As hallmark of TTP, generalized hyaline thrombi in the patient's microcirculation is known. These thrombi are composed of platelets and VWF. A severe defect of the VWF cleaving protease (VWF-CP) was found in all known patients with the inherited form of TTP. In contrary, although a severe deficiency of VWF-CP is specific for the acquired form, too, only a fraction of these patients is characterized by a severe deficiency. In most patients with a severe deficiency autoantibodies directed against VWF-CP is detectable in plasma. However, many patients with acquired TTP do not show any severe deficiency. Because treatment differs in inherited and acquired forms and as persistance of autoantibodies during clinical remission is of prognostic value, the determination of the activity of VWF-CP and of antibodies against VWF-CP are important parts in the workup of patients with TTP. In all methods for the determination of the activity of VWF-CP the first step is proteolysis of a specific substrate for the protease. In the second step the activity of the protease is measured by analysis of the residual VWF multimers, by the generation of specific fragments, by using the residual VWF:CB or VWF:RCo as marker of the loss of multimers or with help of specific monoclonal antibodies. In less than 30 min the cone and plate(let) aggregometer helps to distinguish between different forms of thrombotic microangiopathies. While adhesion and aggregation of platelets from a healthy person are clearly enhanced after addition of a small amount of plasma from a TTP patient, both characteristics are weakened by plasma from patients with other forms of thrombotic microangiopathy (dilution effect). Molecular genetics are established methods in the differentiation between inherited and acquired forms of TTP in those cases without autoantibodies against VWF-CP.     

Ustekinumab associated thrombotic thrombocytopenic purpura

Thrombotic thrombocytopenic purpura (TTP) is a rare disorder. Plasma exchange therapy has been shown to significantly reduce mortality in patients with TTP. Here, we report a case of TTP associated with ustekinumab therapy after a period of 2-3 years. Ustekinumab, a monoclonal antibody that inhibits interleukin 12 and interleukin 23, is one of the newer treatments for psoriasis. Although our patient experienced a prolonged course of TTP requiring 1 month of daily plasma exchange therapy, he recovered and remains in remission after 6 months.     

Update on thrombotic thrombocytopenic purpura

Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy, which is classically associated with signs and symptoms of fever, thrombocytopenia, neurologic deficits, hemolytic anemia, and renal failure. It is caused by a deficiency of A Disintegrin-like And Metalloprotease with a ThromboSpondin type1 motif 13 (ADAMTS13), which may be an inherited disorder, but more commonly is an acquired disease due to autoantibodies directed against ADAMTS13. Low ADAMTS13 levels result in increased ultra-large von Willebrand factor multimers, which induce platelet adhesion and thrombosis. Plasma exchange therapy is the standard of care, and has greatly reduced morbidity and mortality. A recent TTP case is reviewed, and treatments for recurrent or refractory TTP are summarized. A scoring system using clinical and laboratory parameters to evaluate which suspected TTP patients will benefit from plasma exchange therapy is also discussed.     

Chronic relapsing thrombotic thrombocytopenic purpura

A 58-year-old man had anemia and thrombocytopenia immediately after a myocardial infarction; recovery occurred spontaneously, but relapses followed intercurrent infection and abdominal surgery. The terminal relapse was precipitated by gastric ulcer with hemorrhagic gastritis; this episode was characterized by fluctuating neurologic symptoms including coma. Autopsy studies confirmed the diagnosis of thrombotic thrombocytopenic purpura. This case shows that thrombotic thrombocytopenic purpura may occur de novo in adults as a relapsing syndrome with exacerbations precipitated by diverse events characterized by inflammation or tissue necrosis.     

Complement activation in thrombotic thrombocytopenic purpura

Summary. Background: Ultra‐large von Willebrand factor and deficiency of its cleaving protease are important factors in the events leading to thrombotic microangiopathy; however, the mechanisms involved are only partly understood. Whereas pathological activation of the alternative complement pathway is linked to atypical hemolytic uremic syndrome, the role of complement activation in thrombotic thrombocytopenic purpura (TTP) is unknown. The aim of this study was to investigate whether signs of complement activation are characteristic of TTP. Patients and methods: Twenty‐three patients with TTP (18 women, median age 38 years) and 17 healthy controls (13 women, median age 38 years) were included. Complement parameters (C3, Factors H, I, B and total alternative pathway activity) together with complement activation fragments (C3a) or complexes (C1rs‐INH, C3bBbP, sC5b9) were measured by ELISA or RID. ADAMTS13 activity and anti‐ADAMTS13 inhibitory antibodies were measured by the VWF‐FRET73 assay. Results: Increased levels of C3a, and SC5b9 were observed in TTP during acute episodes, as compared with healthy controls. Decreased complement C3 levels indicative of complement consumption occurred in 15% of acute TTP patients. Significant decrease of complement activation products C3a and SC5b9 was observed during plasma exchange (PEX). The sustained presence of anti‐ADAMTS13 inhibitory antibodies in complete remission was associated with increased complement activation. Conclusion: These data document in an observational study the presence of complement activation in TTP. Further investigation is needed to determine its potential pathogenetic significance.     

Seasonal association of thrombotic thrombocytopenic purpura

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP), a thrombotic microangiopathy, is a clinical diagnosis, characterized by microangiopathic hemolytic anemia and thrombocytopenia without another likely explanation. Some initiators of the disease are well represented in the literature, such as certain drugs, malignancies, and viral illness; however, there are less objective factors still being investigated, with references to hormonal, stress, and seasonal variations considered anecdotally. A better insight of these factors would aid in understanding the pathophysiology of the disease. STUDY DESIGN AND METHODS: We performed a retrospective review of all idiopathic TTP cases treated with therapeutic plasma exchange at our institution from 1999 to 2008 to determine whether there was seasonal variation in TTP presentation. Seasons were defined as follows: winter = December to February; spring = March to May; summer = June to August; and fall = September to November. With the use of Poisson regression models, the incidence between seasons was compared. RESULTS: During this study period, a total of 97 cases were recorded. Summer had the highest occurrence of TTP (35%). This was significant compared to the fall (p = 0.012) and the winter (p = 0.019). There were more cases in the summer compared to the spring, but this was not significant. CONCLUSION: In our population, there was a significant difference in the number of TTP cases presenting in summer compared to fall and winter. This supports a possible environmental, infectious, or physiologic influence associated with the summer.     

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.     

Elevated platelet-surface-bound IgM in thrombotic thrombocytopenic purpura

The level of platelet-surface-bound IgM (PSIgM) was measured during the course of therapy in two patients with thrombotic thrombocytopenic purpura (TTP). Before therapy, both had significantly elevated PSIgM. In both cases the PSIgM dropped after the institution of treatment with plasmapheresis, steroids, and dipyridamole, correlating with a complete response to therapy in one patient and a partial response in the second. This is further evidence that in some cases of TTP, an immune mechanism is present.