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Immune thrombotic thrombocytopenic purpura (iTTP) is a rare and potentially life-threatening disorder. Treatment advances have lowered morbidity rates, but past acute events can still cause long-term consequences, reducing health-related quality of life (HRQoL) and determining cognitive impairment, anxiety, and depression. We aimed to investigate these aspects and the role of caplacizumab and rituximab: 39 patients were evaluated using the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), the FACIT-Fatigue, the Hospital Anxiety and Depression Scale, and the Functional Assessment in Cancer Therapy-Cognitive Function questionnaires. The median age at study inclusion was 50 years (IQR 38-60), and the median follow-up from diagnosis was 97 months (IQR 14-182); 82% of patients were female, and 36% had one or more recurrences. Caplacizumab was administered in 16 patients (41%), as well as rituximab. ITTP patients reported lower physical and mental HRQoL scores than the general population. No differences in physical or mental domains were observed between patients treated or not with caplacizumab, while those who received rituximab reported lower scores in mental health. Neurological impairment at diagnosis correlated with worse fatigue. The majority of patients (72%) reported anxiety or depression (82%). ITTP had a significant impact on the long-term cognitive function, fatigue, depression, and anxiety levels of patients, with a negative effect on their HRQoL. Our findings underscore the need to pay special attention to patients' long-term physical and mental health, regardless of the medical treatments received., (© 2024. The Author(s).)

It has been proposed that the onset of Acquired Thrombotic Thrombocytopenic Purpura (iTTP) is more severe than subsequent relapses; however, existing studies have limitations. We conducted a retrospective observational study to compare analytical and clinical severity of onset and relapse aTTP cases between 2012 and 2023. A total of 370 episodes of aTTP were analyzed, comprising 272 at initial diagnosis and 98 relapses. At onset, analytical parameters indicative of severity (low hemoglobin, low platelet count, and increased LDH) were significantly worse; patients had severe neurological symptoms (p<0.001) and ≥ 3 points in the TMA mortality score (p<0.001). In conclusion, the onset of aTTP is associated with worse analytical parameters and severe neurological involvement., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Pregnancy is a well-established trigger for a first episode or relapse of immune thrombotic thrombocytopenic purpura (iTTP). Other outcomes of subsequent pregnancy after a diagnosis of iTTP are less well described. We conducted this retrospective cohort study to evaluate maternal and fetal outcomes of pregnancy in women with prior iTTP from the Johns Hopkins Thrombotic Microangiopathy Cohort. Of 168 women in the cohort, 102 were of reproductive age at diagnosis. Fourteen pregnancies (in 9 women) that occurred after the initial iTTP episode were included in the analysis. iTTP relapse occurred in 9 (64%) pregnancies. Out of the 9 instances of relapse, 5 relapses occurred in 2 women. Seven pregnancies (50%) ended in fetal death or miscarriage in the setting of iTTP relapse and three were electively terminated due to fear of relapse. Four pregnancies (50% of the 8 that progressed beyond 20 weeks) were complicated by preeclampsia or HELLP syndrome, which is over ten-fold higher than that of the general population. No maternal deaths occurred. Only 4 pregnancies resulted in live births, of which, 2 were pre-term. Pregnancy in women with prior iTTP is associated with a substantial risk of iTTP relapse and fetal loss. Preeclampsia and HELLP syndrome is also more common than that in the general population. ADAMTS13 monitoring and preemptive therapy may improve pregnancy outcomes, which needs to be evaluated prospectively., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Despite the effectiveness of plasma exchange (PEX) and immunosuppressants in the treatment of acquired thrombotic thrombocytopenic purpura (aTTP), a number of patients still die as a result of the disease. Whether caplacizumab could rescue these patients remains still unsettled. The objective of this study was to characterise mortality patterns and prognostic factors in the first episode of aTTP.We queried the Spanish TTP Registry for patients with a diagnosis of aTTP in their presenting episode who fulfilled complete clinical and follow-up data (n = 102). The patients were diagnosed between 2004 and 2018, and all were treated with daily PEX and corticosteroids. Clinical and laboratory data were analysed at diagnosis and during the treatment course.Eight patients (7.7%) died between 12 h and 36 days after presentation, and could be classified into three patterns: death before treatment, early death driven by acute cardiac or neurologic events, and late death due to unremitted aTTP. Stupor or coma at diagnosis and platelet count < 20 × 10 9 /L by the 6th treatment day were independently associated with increased risk of death.Stupor or coma at diagnosis and lack of response to PEX by the 6th day in patients experiencing the first episode of aTTP are strong predictors of mortality. These patients could be rescued by novel agents aimed at halting the microvascular thrombosis until adequate immunosuppression is achieved., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Thrombotic thrombocytopenic purpura (TTP) is fatal in 90% of patients if left untreated and must be diagnosed early to optimize patient outcomes. However, the very low incidence of TTP is an obstacle to the development of evidence-based clinical practice recommendations, and the very wide variability in survival rates across centers may be partly ascribable to differences in management strategies due to insufficient guidance. We therefore developed an expert statement to provide trustworthy guidance about the management of critically ill patients with TTP. As strong evidence was difficult to find in the literature, consensus building among experts could not be reported for most of the items. This expert statement is timely given the recent advances in the treatment of TTP, such as the use of rituximab and of the recently licensed drug caplacizumab, whose benefits will be maximized if the other components of the management strategy follow a standardized pattern. Finally, unanswered questions are identified as topics of future research on TTP.

Therapeutic plasma exchange (TPE) has dramatically improved the prognosis of acquired thrombotic thrombocytopenic purpura (TTP), and TPE and corticosteroids are the mainstays of treatment of acquired TTP. However, a subset of patients may remain refractory to this treatment modality, or have an initial response but relapse after the discontinuation of TPE during the follow-up. While managing patients with relapsed/refractory acquired TTP, there are several therapeutic maneuvers, which can be considered. Recently, there came some papers regarding the use of bortezomib in relapsed or refractory acquired TTP, and in this review, this indication of bortezomib was evaluated along with the current data available. In seven published papers, 12 patients with relapsed/refractory acquired TTP received bortezomib, of which 11 survived the acute episodes and maintained remission. Bortezomib may serve as an adjunct treatment, but prospective trials are needed to determine the dosing, administration route, and the treatment schedule of this treatment option in patients with relapsed/refractory TTP.

Thrombotic thrombocytopenia purpura (TTP) and atypical hemolytic uremic syndromes (aHUS) are distinct clinical disorders characterized by hemolytic anemia, thrombocytopenia, microthrombi, and end organ damage. TTP is characterized by a low ADAMTS13 activity level at diagnosis of <10 % ADAMTS13 activity, while aHUS is characterized as having >10 % ADAMTS13 activity. Despite clinical remission, survivors of thrombotic microangiopathy suffer significant comorbidity and decreased quality of life (QOL) than their healthy counterparts. The reason for this is unclear. Is it a lingering effect from their initial acute episode or ongoing subclinical injury/inflammation despite clinical remission? Common clinical complaints validated in practice include increased depression, deficits in memory, concentration, mood, and mental endurance. We suspect headaches may be an important clinical tool toward understanding patient morbidity and decreased QOL. To date, no studies report headache frequency or severity in this population. To answer this question, adult patients >3 months since their last acute episode of TTP or aHUS were approached to take a Headache Impact Test (HIT-6) survey. Between June 1, 2013 and May 30, 2014, 31 patients in remission (21 patients with prior TTP and 10 patients with prior aHUS) completed the HIT-6 survey. The survey scores were then compared to the HIT-6 normative population data established by Qualitymetric incorporated. Overall, TTP patients had a significantly higher average HIT-6 score of 59.9 compared to an average HIT-6 score of 51 seen in sex-matched controls (SD 9.6, p value 0.002). No significant difference was seen in the HIT-6 scores of aHUS patients. Of TTP patients studied, approximately 57 % (12/21) had three or more episodes and were >24 months since the last episode. The average time since last acute episode in TTP patients was 37.5 months. There was no significant correlation between TTP survivor HIT-6 scores and the number of prior episodes (1, 2, or >3) or timing from the last episode (3-6, 7-12, 13-24, or >24 months). About 19/21 (90 %) patients, who are TTP survivors, also had a normal ADAMTS13 activity level (>10 %) on the day of the survey. Our study suggests that headaches have significant impact on TTP survivors and should be followed in the clinical setting to prevent undue patient morbidity. Larger studies are needed to understand how headaches impact long-term survival and risk of relapse.

Current guidelines advise against the transfusion of platelets in patients with thrombotic thrombocytopenic purpura (TTP) except in cases of life-threatening hemorrhage. We conducted a retrospective medical chart review to examine the outcomes of patients with TTP who received platelet transfusion at our institution from September 2002 to September 2012. A search for "thrombotic thrombocytopenic purpura" in the discharge summary identified 233 patients, out of which only 15 patients had TTP and received platelet transfusion. Primary outcomes were death due to any cause, myocardial infarction, ischemic stroke, coma, seizure, or worsening neurologic status within 24 h of platelet transfusion. Secondary outcomes included bleeding and worsening thrombocytopenia. No adverse outcomes occurred within 24 h of platelet transfusion. Two patients experienced bleeding following renal biopsy despite having platelet counts of greater than 50,000/μl and receiving one pack of pooled platelets prior to the procedures. The response to transfusion was variable. In general, platelet transfusion was not detrimental in this population; however, the efficacy is uncertain.

Introduction: The prognosis of thrombotic thrombocytopenic purpura (TTP) has considerably improved since the introduction of plasma exchange (PEX) therapy. However, unresponsive thrombotic thrombocytopenic purpura (Un-TTP) still carries high morbidity and mortality rates, indicating a need for early specific treatments., Patients and Methods: In a retrospective study including consecutive adults with TTP admitted between January 1997 and January 2011 in a teaching hospital intensive care unit (ICU), our objective here is to identify early clinical and laboratory features predicting Un-TTP. Patients who responded to plasma exchange and steroids (N = 49) were compared with patients with unresponsive TTP defined as requirement for other treatments, protracted course, or death (N = 37, 43 %)., Results: Hospital mortality was 24.3 % in the Un-TTP group. Variables associated with Un-TTP on univariate logistic regression were older age, cardiac involvement, neurological involvement, higher anti-a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS13) immunoglobulin G (IgG) titer, lower platelet counts starting on day 2, higher Sequential Organ Failure Assessment (SOFA) scores starting on day 3, need for higher plasma volumes to obtain remission, and greater use of adjuvant treatments and life-sustaining interventions. Multivariate logistic regression identified four factors independently associated with Un-TTP: age over 60 years [odds ratio (OR) 7.90; 95 % confidence interval (95 % CI) 1.06-78.34], cardiac (OR 5.17; 95 % CI 1.63-16.39) or neurological (OR 8.04; 95 % CI 1.27-51.03) manifestations at diagnosis, and day 2 platelet count less than 15 G/l (OR 3.88; 95 % CI 1.30-11.62)., Conclusion: Therapeutic intensification starting on day 3 or even earlier in patients with the independent risk factors for unresponsive TTP identified in our study deserves evaluation in a multicenter prospective study.

The remission rate with plasma exchange (PE) in thrombotic thrombocytopenic purpura (TTP) exceeds 80%, but the disease relapses in up to 20-30% of the cases. Clinical characteristics and response to treatment of relapsed TTP are not well defined. The objective of the present study was to compare the clinical and biological characteristics at presentation and the response to treatment between de novo and relapsed TTP. For such purpose, a total of 102 episodes of idiopathic TTP (70 de novo and 32 relapses) included in a recent multicentric prospective cohort study were analysed. All patients were homogeneously treated with daily PE and costicosteroids. In comparison with de novo TTP, episodes of relapsed TTP showed a higher Hb level (median, 122 g/l versus 91 g/l, p < 0.001) and lower serum lactate dehydrogenase (2.2- versus 4.5-fold above the upper limit of normality, p < 0.001). Neurological symptoms and fever were less frequently observed in patients with relapsed TTP than in patients with de novo TTP. Patients with relapsed TTP needed fewer PE sessions (five versus ten, p = 0.02) and a smaller volume of plasma (221 ml/kg versus 468 ml/kg, p = 0.004) to achieve remission than those with de novo TTP. There was no significant difference in the rate of recrudescence under treatment, the need of complementary treatments or the frequency of refractoriness to PE therapy. In conclusion, relapsed TTP has a milder clinical profile and responds more easily to PE than de novo TTP.

For some time now, there have been reports of acral necrosis as a paraneoplasia that may occur in association with a number of different malignant tumours. There have also been a series of reports about acral necrosis associated with chemotherapy with various cytostatics. The treatment of choice if these lesions occur is plasmapheresis. Ultimately, the occurrence of thrombotic microangiopathy (TMA) can only be prevented by close monitoring through regular laboratory controls before each new cycle of chemotherapy. In the differential diagnosis, Raynaud's syndrome should be considered as a premonitory paraneoplasia, a risk factor for the occurrence of acral necrosis in patients with a malignant tumour undergoing chemotherapy, particularly patients with ovarian carcinoma receiving gemcitabine treatment.

Hereditary thrombotic thrombocytopenic purpura (TTP) is a rare disorder characterized by occlusive microvascular thrombosis, consumptive thrombocytopenia, and microangiopathic hemolytic anemia. Homozygous or compound heterozygous mutations in the ADAMTS13 gene result in a congenital severe ADAMTS13 deficiency and subsequent accumulation of ultra-large von Willebrand factor multimers, which tend to form platelet thrombi in the microcirculation. We report a first case of congenital TTP on the African continent with a new, homozygous mutation in the metalloprotease domain of ADAMTS13. An initially oligo-symptomatic presentation was followed by acute exacerbation with ischemic stroke and acute renal failure highlighting the severity of this syndrome.

Thrombotic thrombocytopenic purpura (TTP) or Moschowitz's syndrome is characterized by release of unusually large von Willebrand factor (ULvWF) multimers and a deficiency of vWF metalloprotease. It is a very rare condition, but it causes serious problems. The etiology is still unknown, although surgical stress has been associated with TTP, probably by releasing massive amounts of ULvWF. TTP is an acute, recurrent disease of the circulatory system, consisting of thrombocytopenia, microangiopathic hemolytic anemia, fever, neurological signs, and renal dysfunction. It has the strong possibility of being fatal and thus should be treated immediately, mostly by plasmapheresis. We report a case of TTP following a high tibial valgus osteotomy. An association between TTP and orthopedic surgery--as far as we know--has only once been reported in the literature. We suggest that orthopedic surgeons should be aware of this because, although very rare, postsurgical TTP could be a life-threatening postoperative complication, which needs prompt diagnosis and treatment.

Objective: Thrombotic microangiopathies, namely thrombotic thrombocytopenic purpura and hemolytic uremic syndrome, are uncommon microvascular occlusive diseases. Despite the dramatic improvement in the outcome by exogenous plasma supply, either through plasma infusion or through plasma exchange, patients frequently require support in the intensive care unit. In the present study, we evaluated the outcome of a large cohort of patients with severe thrombotic microangiopathies., Design: A retrospective multicenter study from January 1998 to June 2001., Setting: Fourteen French university hospital medical intensive care units., Patients: Sixty three adult patients with severe thrombotic microangiopathies., Measurements and Results: Of the 63 patients, 19 had a clinical presentation of thrombotic thrombocytopenic purpura, 18 had hemolytic uremic syndrome and 26 had combined neurologic and renal failures. Infections were the main etiology associated with thrombotic microangiopathies. The mortality rate was 35%. Of the survivors, all achieved complete remission. Whereas neurologic failure assessed through the Glasgow coma scale was an independent predictor of mortality [HR=0.845 (CI 95%: 0.759-0.940), P=0.002], renal impairment did not appear to be an adverse prognostic factor. The use of plasma exchange was independently associated with survival [HR=0.269 (CI 95%: 0.104-0.691), P=0.006]., Conclusions: Thrombotic microangiopathies with severe organ dysfunctions leading to hospitalization in the intensive care unit are associated with high mortality. Neurologic impairment appears to be the main adverse prognostic factor correlated to mortality, and the study confirms the importance of plasma exchange in the treatment of high-risk patients.

Thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy. Besides anemia and thrombocytopenia, neurological impairment is common in TTP. A 42-year-old woman was admitted to a department of obstetrics/gynecology because of severe vaginal bleeding due to thrombocytopenia. After platelet transfusion, the patient developed a reduced level of consciousness, confusion, headache, and fever. CT scan did not show pathological changes. Transcranial Doppler sonography revealed increased blood flow velocities of all basal cerebral arteries. Because encephalitis was suspected the patient was transferred to the neurological department. CSF and cerebral magnetic resonance imaging studies were normal. Finally, the detection of schistocytes in the peripheral blood smear and the strong elevation of LDH led to the diagnosis of TTP. After plasma exchange over 3 consecutive days the patient achieved complete remission. The diagnosis was confirmed by laboratory tests (activity of ADAMTS13 <5%, IgG antibodies against ADAMTS13). Platelet transfusion may adversely affect the outcome of patients with suspected TTP. Severely deficient activity of the von Willebrand factor cleaving protease (ADAMTS13) is specific for thrombotic thrombocytopenic purpura.

Objective: To report on the development and treatment of thrombotic microangiopathy, an atypical cause of acute renal failure in patients with acute pancreatitis., Design: Case reports., Setting: A 21-bed medical intensive care unit at an university hospital., Patients: Two men with acute pancreatitis presented with acute renal failure, neurological manifestations, haemolytic anaemia and thrombocytopenia. Both patients required intensive care., Measurements: Fragmented red cell count; levels of haptoglobin, amylase and lipase; serological testing for Escherichia Coli O157; computed tomography of the abdomen., Main Results: The patients' courses were rapidly favourable after daily plasma exchange. A review of the existing medical literature was also undertaken., Conclusion: As thrombotic microangiopathy may be life-threatening without administration of fresh frozen plasma or plasma exchange, physicians should consider this disease as a possible cause of acute renal failure in patients with acute pancreatitis.

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.

Objective: Thrombotic microangiopathy (TMA) has been associated with a large number of underlying diseases. We conducted a descriptive, retrospective study including all TMA adult patients admitted to our ICU, with a particular interest in infectious episodes as a trigger of TMA., Patients: All adult patients (30) with a diagnosis of TMA admitted to the medical ICU at Saint-Louis Hospital (Paris, France) between 1992 and 1998 were retrospectively included., Methods: All patients with clinical and microbiological evidence of bacterial infection were treated with intravenous antibiotics. The specific treatment of TMA consisted in solvent/detergent-treated plasma administration by plasma exchange or high volume plasma infusion (30 ml/kg per day) in fractionated doses., Results: Among the 30 adult patients studied, TMA in 16 (53%) was associated with microbiologically documented infection. An acute infection was found in 8/9 patients with an HIV-related TMA, in 2/6 patients with a systemic lupus erythematosus (SLE)-related TMA and in 3/6 patients with TMA associated with other disorders. In three patients, an acute infectious disease was the only cause associated with the TMA. Four other patients had clinical manifestations suggesting an infection process but without bacteriological documentation. Escherichia coli was isolated in 7/16 cases and verotoxin was found in the stools of two other patients. All patients were treated with plasma administration and those with evidence of infection were systematically and intensively treated with antibiotics. Eventually 8 patients died (27%), 20 (67%) reached complete remission and 2 partial remission., Conclusion: Bacterial infections are commonly observed amongst TMA patients hospitalized in ICUs and may act as a trigger of this disease. Screening for infection is a requirement in patients with TMA, either idiopathic or associated with other conditions.

Results of treatment of 18 patients fulfilling the criteria for TTP are presented. Thrombocytopenia was present in all patients (100%). Sixteen of the 18 patients (88.8%) had mental status changes, and seven of the 18 patients (38.8%) had renal impairment. One patient had a secondary type of TTP, caused by non-Hodgkin's lymphoma of the large intestine (that was diagnosed later) and was excluded from the study. Immunosuppresive therapy with steroids, plasma exchange and replacement of removed volume with fresh frozen plasma in a dosage of 25 ml/kg body weight resulted in a statistically significant increase of platelet count (P = 0.00222), and a significant improvement in consciousness defined by increased GCS after 2 weeks (P = 0.00222). In two patients renal function recovered, and in one of them hemodialysis was no longer needed. This improvement in a small group of patients had no statistical significance. TTP recurred in seven patients. High doses of steroids caused serious side effects in two patients: in one patient, steroid diabetes, and in the other one, intestinal perforation.

An 81-year-old man was admitted to the hospital with a fever and loss of appetite. After treatment with piperacillin sodium (PIPC), the patient exhibited thrombocytopenia, hemorrhagic colitis, and drug-induced skin eruption. On the fifth day after PIPC induction, he further experienced neurological abnormalities, such as disorientation and confusion, renal dysfunction, and microangiopathic hemolytic anemia (MAHA). The patient was diagnosed with thrombotic thrombocytopenic purpura (TTP) on the basis of thrombocytopenia, MAHA, renal dysfunction, fever, and neurological abnormalities. Infusion of fresh-frozen plasma was initiated for treatment. His condition improved markedly after this treatment. It is rare for TTP to be accompanied with hemorrhagic colitis and skin eruption. These symptoms were induced by PIPC and were successfully treated with plasma infusion.

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.

The thrombotic thrombocytopenic purpura/ hemolytic uremic syndrome (TTP/HUS) is a rare disorder characterized by microangiopathic hemolysis and thrombocytopenia. We have undertaken a retrospective analysis of the clinical characteristics, treatment outcome, and prognosis of 48 patients diagnosed and treated in our institution during a 13-year period. Among our patients 22 (46%) had fever, 35 (73%) neurological abnormalities, and 22 (46%) renal impairment at presentation of the syndrome. All patients were treated with a multimodality regimen including plasma exchange, steroids, antiplatelet agents, and IgG infusion. Of the 48 patients, 41 achieved complete remission, two had a partial response, and five had no response and died of progressive disease. Within a median follow-up period of 40 months, ten of the 41 patients who had achieved remission relapsed, most of them within the first 2 years, and nine of these responded promptly to plasma exchange therapy. Eight deaths were observed, seven of refractory disease and one in fourth relapse. The analysis of prognostic factors revealed advanced age and severe renal impairment (creatinine levels above 2 mg%) as the only parameters associated with treatment failure and poor outcome. However, none of the pretreatment characteristics proved to be of prognostic value regarding the probability of relapse. In conclusion, TTP/HUS represent a syndrome of variable clinical expression and aggressiveness. The use of a multimodality regimen in our series produced a high response rate. Nevertheless, the early identification, based on clinical characteristics, of poor-prognosis cases that probably need more or alternative forms of treatment is an issue that remains to be elucidated in prospective trials.

The combination of sickle cell disease crisis and thrombotic thrombocytopenic purpura has been described only a few times. Here we present the case of a patient with a hemolytic crisis due to sickle cell disease complicated by thrombotic thrombocytopenic purpura. We also review the cases previously reported and compare and contrast them, highlighting diagnostic challenges.

Unlabelled: The pentad of thrombocytopenia, haemolytic anaemia, mild renal dysfunction, neurological signs and fever, classically characterizes the syndrome of thrombotic thrombocytopenic purpura (TTP). TTP usually occurs in adults but also children have been described with this condition. The disorder may take a relapsing course, termed chronic relapsing TTP (CRTTP), which although very rare, may also begin in childhood. Deficiency of a recently identified enzyme, the von Willebrand factor (vWF)-cleaving protease, seems to play a major role in the development of TTP. We report on a 3-year-old boy with a dramatic but typical clinical course of CRTTP. At the time of diagnosis, neurological deficits and multiple cerebral infarctions had already occurred. In plasma, vWF-cleaving protease was completely absent, both during acute TTP and in remission. There was no protease inhibitor detected. Regular infusions of fresh frozen plasma were successfully given for replacement on a prophylactic basis., Conclusion: Assay of von Willebrand factor-cleaving protease helps to diagnose a form of thrombotic thrombocytopenic purpura which may be managed by prophylactic treatment with fresh frozen plasma.

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.

Chronic relapsing thrombotic thrombocytopenic purpura (CRTTP) is the rarest type of TTP, usually presenting in childhood. The aetiology is still not fully explained. The disorder is associated with the presence in plasma of unusually large von Willebrand factor (UlvWF) multimers that are especially prominent between episodes. CRTTP can be prevented by periodic plasma transfusions. We report three children with congenital CRTTP who have been successfully treated and maintained in prolonged remission by the prophylactic use of fresh frozen plasma without concurrent plasmapheresis. Two of the patients are sibs.

Objective: Description of diagnostic procedures, treatment modalities and intensive care management of patients with thrombotic thrombocytopenic purpura (TTP)., Design: Descriptive study., Setting: Internal medicine Intensive Care Unit (University Hospital of Vienna)., Patients: Six patients (two after allogeneic bone marrow transplantation), treated for 12 episodes of TTP., Interventions: Treatment with plasma exchange (fresh frozen plasma, 50-80 ml/kg per day), prednisone (0.75 mg/kg b.i.d.) and, in some cases, vincristine. Supportive therapy as needed., Measurements and Results: Patients were admitted to the ICU because of neurological symptoms with acute onset (42% mild, 58% severe), hemolysis and thrombocytopenia. Additional symptoms were fever (50%), bleeding tendency (50%), acute renal failure (42%) and metabolic derangement (8%). Initial laboratory values showed thrombocytopenia (median 17 G/l), hemolysis (median hemoglobin 10.0 g/dl, lactate dehydrogenase 635 U/l, reticulocyte count 175 G/l) with red cell fragmentation. Coagulation tests were normal. Respiratory assist was needed in six episodes (severe seizures, cardiopulmonary resuscitation). In patients without preexisting hematological abnormality the platelet counts exceeded 100 G/l after 3-8 cycles of plasma exchange. In patients after bone marrow transplantation, the platelet counts never exceeded 40 G/l, but the lactate dehydrogenase levels dropped significantly. The neurological symptoms disappeared in all patients and renal function normalized. One patient died before the initiation of therapy. Three patients relapsed 1-3 times between 2 weeks and 5 months after the last episode. The relapses were associated with symptoms similar to the first episode and responded promptly to plasma therapy., Conclusions: TTP is a rare, but life-threatening disorder. It needs immediate diagnosis and has a good prognosis after adequate treatment with plasma exchange.

The aim of this study was to investigate pretreatment prognostic factors that could be useful in predicting the response to plasma exchange in thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS). Thirty-two patients with TTP/HUS, treated with plasma exchange at our institution from 1980 to 1994, were studied. The main clinical and laboratory data at the beginning of plasma exchanges were analyzed by the Cox stepwise logistic regression, applied to either treatment failure or death. Seventeen (53%) patients attained a complete remission and 22 (69%) survived (five in advanced renal failure and long-term hemodialysis). Longer delay in initiating plasma exchanges, presence of stupor or coma, and higher creatinine levels at the beginning of plasma exchanges were independent predictors of treatment failure. Stupor or coma at the beginning of plasma exchanges was the only predictor of mortality from unremitted TTP/HUS. Hemoglobin levels, platelet count, and LDH activity, traditionally envisaged as markers of disease activity, neither correlated with previous duration of TTP/HUS nor had any prognostic value. Early diagnosis of TTP/HUS and prompt initiation of intensive plasma exchange emerged from this study as the most effective interventions for improving the prognosis of TTP/HUS patients.

An adolescent girl with severe thrombotic thrombocytopenic purpura (TTP) remained in a critical condition after 3 weeks of combined treatment with antiplatelet drugs, plasma infusions and plasma exchange. The introduction of vincristine resulted in gradual improvement and eventual complete remission which lasted for 2 years. When she relapsed, immediate improvement was observed with the combined treatment of plasmapheresis and vincristine. She has now been in complete remission again for 10 months. It is suggested that plasmapheresis plus vincristine should be used as the initial treatment for children with TTP.

Thrombotic thrombocytopenic purpura (TTP) is a hematologic disorder which is clinically characterized by thrombocytopenia, microangiopathic hemolytic anemia, fever, neurologic symptoms, and cardiac and renal involvement. The pathogenic mechanisms of this disease are poorly understood. It is well known that TTP is associated with pregnancy and that prognosis for the mother and child is poor. We present the first case of a severe TTP diagnosed in the first trimester of pregnancy (13th week of gestation) with maternal survival and birth of a healthy child which required continuous and intensive treatment with plasma therapy until delivery. During a period of 24 weeks several attempts to discontinue plasma therapy failed because of continuous active disease, and it became evident that plasma infusions were not as effective as plasma exchanges. The fact that the patient entered into remission soon after delivery of a healthy child by cesarean section in the 37th gestational week shows that in this case pregnancy activated an unknown factor which does not cross the placenta and which can be removed by plasmapheresis.

We report a case of thrombotic thrombocytopenic purpura which responded spectacularly to therapy consisting of corticosteroids, prostacyclin, high doses of platelet anti-aggregants and repeated plasma exchange. There was no anomaly of the von Willebrand factor VIII. The number of schizocytes and the lactate dehydrogenase level are as important as the beta-thromboglobulin dosage.

We report two patients with thrombotic thrombocytopenic purpura who were subjected to plasma exchange. In one case, the plasma levels of platelet factor 4, measured shortly after plasma exchange, increased significantly during plasma exchange. This was followed, however, by a failure to respond to therapy. Repeated plasmapheresis over 3 weeks gave no therapeutic benefit and reversible deep coma occurred. This patient recovered completely after treatment with vincristine. In the second patient, a decline in platelet factor 4 was observed after plasma exchange. This was accompanied by improvement of the patient's condition and a slow rise in platelet count. Plasma exchange was again carried out in this patient because of a recurrence of thrombotic thrombocytopenic purpura 3 years later; again decreased platelet factor 4 plasma levels were observed after plasma exchange and again a therapeutic response followed. Platelet factor 4, therefore, seems to be an effective and early index for the therapeutic benefit of plasma exchange in thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura (TTP) is an uncommon disorder which usually occurs in young adults. It is characterized by a pentad of clinical findings: fever, neurological abnormalities, renal dysfunction, microangiopathic hemolytic anemia and thrombocytopenia. The histological hallmark is the presence of platelet thrombi occluding the microcirculation of multiple organs. The etiology and pathogenesis of disseminated platelet aggregation are uncertain and obviously not uniform in individual patients. Experimental findings suggest that microthrombi may result from intravascular platelet activation or form secondarily at sites of vessel wall damage. The differential diagnosis of TTP includes the hemolytic uremic syndrome in which the microangiopathic changes are exclusively found in the kidneys. When untreated, TTP invariably runs a progressive and fatal course. In recent years, prognosis has been improved by new forms of therapy such as plasmapheresis or infusions of fresh frozen plasma which may lead to recovery in about 80% of patients.

Moschcowitz syndrome or thrombotic thrombocytopenic purpura is a rare disorder with a poor prognosis. This syndrome is characterized by a microangiopathic hemolytic anemia with thrombocytopenia, neurologic symptoms and renal disease. The vascular lesion consists of disseminated hyaline thrombi in the microvasculature composed mainly of platelet aggregates. The mechanisms are still poorly understood and are probably multiple. Recent data focus on an abnormal endothelial synthesis of prostacyclin and the presence of a factor (or the reduction of its inhibitor) in plasma able to induce intravascular disseminated platelet aggregation. The most efficient therapy seems to be infusions of fresh plasma with or without plasma exchange.