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1.
Schneppenheim R Budde U Oyen F Angerhaus D Aumann V Drewke E Hassenpflug W Häberle J Kentouche K Kohne E Kurnik K Mueller-Wiefel D Obser T Santer R Sykora KW 《Blood》2003,101(5):1845-1850
Thrombotic thrombocytopenic purpura (TTP) is caused by the persistence of the highly reactive high-molecular-weight multimers of von Willebrand factor (VWF) due to deficiency of the specific VWF-cleaving protease (VWF-CP) ADAMTS13, resulting in microangiopathic disease. The acquired form is caused by autoantibodies against VWF-CP, whereas homozygous or compound heterozygous mutations of ADAMTS13 are responsible for recessively inherited TTP. We investigated 83 children with hemolytic or thrombocytopenic episodes with or without additional neurologic symptoms or renal failure. The presumed diagnosis was chronic idiopathic thrombocytopenic purpura (ITP; n = 50), TTP (n = 8), hemolytic uremic syndrome (HUS; n = 24), and Evans syndrome (n = 1). A severe deficiency of VWF-CP (< or = 5%) was found in all investigated patients with TTP and in none of those with HUS. Additionally, 2 of 50 patients with a prior diagnosis of ITP were deficient for VWF-CP. Antibodies against VWF-CP were found in 4 children. Mutation analysis of the ADAMTS13 gene in the patients deficient in VWF-CP by direct sequencing of all 29 exons identified 8 different mutations, suggesting the hereditary form of TTP in 1 patient with ITP, in the patient with Evans syndrome, and in 5 of the 8 patients with TTP. The phenotype of TTP in childhood can be rather variable. Besides the classical clinical picture, oligosymptomatic forms may occur that can delay the identification of patients at risk. 相似文献
2.
The most common form of isolated thrombocytopenia is idiopathic thrombocytopenic purpura (ITP) in childhood. Hence, pediatricians
consider a possible diagnosis of ITP in patients with isolated thrombocytopenia who are admitted to hospital with complaints
of skin findings such as petechiae, purpura, and ecchymosis. It is well known that cobalamin deficiency may also cause thrombocytopenia
together with anemia and leukopenia in children. However, isolated thrombocytopenia due to cobalamin deficiency has rarely
been reported in literature. In this case report, we present a 7-year-old female patient with isolated thrombocytopenia that
was improved by cyanocobalamin therapy. 相似文献
3.
Thrombotic thrombocytopenic purpura with severe ADAMTS-13 deficiency in two patients with primary antiphospholipid syndrome 总被引:5,自引:0,他引:5
Amoura Z Costedoat-Chalumeau N Veyradier A Wolf M Ghillani-Dalbin P Cacoub P Meyer D Piette JC 《Arthritis and rheumatism》2004,50(10):3260-3264
Arterial thrombotic events, thrombocytopenia, and hemolytic anemia with schistocytes may be encountered in the setting of both thrombotic thrombocytopenic purpura (TTP) and primary antiphospholipid syndrome (APS). We report 2 cases of TTP occurring in patients with definite primary APS. We also describe the results of tests for ADAMTS-13 activity in 20 consecutive patients with primary APS, as well as tests for antiphospholipid antibodies in 26 patients who had TTP, severe ADAMTS-13 deficiency, and ADAMTS-13-inhibiting antibodies. In both of the patients with primary APS and TTP, ADAMTS-13 activity was undetectable, and ADAMTS-13-inhibiting antibodies were present. None of the 26 patients with TTP and severe ADAMTS-13 deficiency was positive for the lupus anticoagulant. One of these patients had a low level of anticardiolipin antibodies (22 IgG phospholipid units). In the 20 patients with primary APS, mean ADAMTS-13 activity was 116% (range 44-250%), and no severe deficiency (< 5%) was observed. Our findings suggest that primary APS must be added to the list of autoimmune disorders that can be complicated by TTP. 相似文献
4.
Zahir Amoura Nathalie Costedoat‐Chalumeau Agns Veyradier Martine Wolf Pascale Ghillani‐Dalbin Patrice Cacoub Dominique Meyer Jean‐Charles Piette 《Arthritis \u0026amp; Rheumatology》2004,50(10):3260-3264
Arterial thrombotic events, thrombocytopenia, and hemolytic anemia with schistocytes may be encountered in the setting of both thrombotic thrombocytopenic purpura (TTP) and primary antiphospholipid syndrome (APS). We report 2 cases of TTP occurring in patients with definite primary APS. We also describe the results of tests for ADAMTS‐13 activity in 20 consecutive patients with primary APS, as well as tests for antiphospholipid antibodies in 26 patients who had TTP, severe ADAMTS‐13 deficiency, and ADAMTS‐13–inhibiting antibodies. In both of the patients with primary APS and TTP, ADAMTS‐13 activity was undetectable, and ADAMTS‐13–inhibiting antibodies were present. None of the 26 patients with TTP and severe ADAMTS‐13 deficiency was positive for the lupus anticoagulant. One of these patients had a low level of anticardiolipin antibodies (22 IgG phospholipid units). In the 20 patients with primary APS, mean ADAMTS‐13 activity was 116% (range 44–250%), and no severe deficiency (<5%) was observed. Our findings suggest that primary APS must be added to the list of autoimmune disorders that can be complicated by TTP. 相似文献
5.
Thrombotic thrombocytopenic purpura (TTP) and haemolytic uraemic syndrome (HUS) are today often regarded as variants of one syndrome denoted as TTP/HUS, characterized by thrombocytopenia caused by intravascular platelet clumping, microangiopathic haemolytic anaemia, fever, renal abnormalities and neurological disturbances. Unusually large von Willebrand factor multimers have been observed in plasma from patients with chronic relapsing forms of TTP. Their appearance in patients with classic TTP is caused by deficiency of a specific von Willebrand factor-cleaving protease. A constitutional deficiency of this protease has consistently been found in familial cases of TTP, whereas in acquired TTP the protease deficiency is caused by the presence of an inhibiting autoantibody. A normal activity of von Willebrand factor-cleaving protease has been established in patients with HUS. In this chapter, we report 23 cases with severe constitutional protease deficiency: about one half of these patients had their first acute episode as children, whereas the other half had their first TTP event at an adult age, several of them during their first pregnancy. Two of these 23 individuals with congenital protease deficiency, both older than 35 years, have never had an acute TTP event. These results indicate that a deficiency of von Willebrand factor-cleaving protease alone is not sufficient to cause acute TTP. Patients with long-lasting dormant protease deficiency have been found to experience multiple relapses of TTP after having had their first acute episode. In one protease-deficient, plasma-dependent patient with chronic relapsing TTP, we estimated that 5% of normal protease activity is sufficient to remove the most adhesive von Willebrand factor multimers and prevent the formation of platelet microthrombi. The deficiency of von Willebrand factor-cleaving protease is a very strong risk factor for TTP, but the development of an acute bout requires a trigger, possibly causing the activation or apoptosis of endothelial cells in the microcirculation. It is unclear whether anti-endothelial cell antibodies, cytokines or other agents are involved in triggering thrombotic microangiopathy. The release of platelet calpain (and/or other proteases), leading to a degradation of von Willebrand factor and to platelet aggregation, has been reported in patients during their acute TTP episode. It is unknown whether calpain directly triggers an acute event or whether it merely reflects its release during the aggregation of platelets by the unusually large von Willebrand factor multimers. With regard to the heterogeneous aetiology of thrombotic microangiopathies, requiring distinct therapeutic measures, a new classification of thrombotic microangiopathy should replace the current, frequently inappropriate clinical discrimination between TTP and haemolytic uraemic syndrome. 相似文献
6.
Thrombotic thrombocytopenic purpura associated with von Willebrand factor-cleaving protease (ADAMTS13) deficiency in children 总被引:4,自引:0,他引:4
Loirat C Veyradier A Girma JP Ribba AS Meyer D 《Seminars in thrombosis and hemostasis》2006,32(2):90-97
The physiopathology of thrombotic thrombocytopenic purpura (TTP) has been clarified since 1998, when it was shown that TTP in adults was most often associated with an acquired deficiency of von Willebrand factor-cleaving protease (ADAMTS13) due to autoantibodies, whereas TTP in children was most often associated with a hereditary autosomal recessive severe deficiency of ADAMTS13. The hereditary form of TPP (Upshaw-Schulman syndrome) is a very rare but life-threatening disease if adequate treatment (plasma therapy) is not administered. First manifestations occur before age 10 in two thirds of cases and as soon as birth in most cases. The subsequent course is characterized by recurrent hemolytic and thrombocytopenic crises, with intervals between relapses from every 3 to 4 weeks in two thirds of cases to several months or years in one third of cases. TTP crises are associated with cerebral vascular accidents in at least 30% of patients, with a risk of neurologic sequelae in approximately 20% of patients. Renal involvement includes frequent acute renal failure due to hemoglobinuria and/or thrombotic microangiopathy during hemolytic crisis and progressive renal deterioration in approximately 50% of cases, leading to chronic or end-stage renal failure in approximately 20% of patients. The clinical phenotype may vary from the typical congenital recurrent TTP. Some mild forms are limited to a fluctuating thrombocytopenia and may be misdiagnosed as idiopathic thrombocytopenic purpura. Phenotypic variability may be observed within a single family, which suggests a role of modifier genes. Fresh frozen plasma (FFP) replaces active ADAMTS13. Ten milliliters per kilogram FFP every 2 to 4 weeks suffices to maintain remission. FFP infusions are best used preventively, given that rescue infusions may not prevent central nervous system and renal involvement. It is hoped that plasmatic or recombinant purified ADAMTS13 will be available in the years to come. 相似文献
7.
Von Willebrand factor-cleaving protease (ADAMTS13) in thrombocytopenic disorders: a severely deficient activity is specific for thrombotic thrombocytopenic purpura 总被引:32,自引:8,他引:24
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A severe deficiency in von Willebrand factor-cleaving protease (ADAMTS13) activity (< 5% that in normal plasma) has been observed in most patients with a diagnosis of thrombotic thrombocytopenic purpura (TTP) but not in those with a diagnosis of hemolytic uremic syndrome. However, ADAMTS13 deficiency has been claimed not to be specific for TTP, since it was observed in various thrombocytopenic and other conditions. We studied 68 patients with thrombocytopenia due to severe sepsis or septic shock (n = 17), heparin-induced thrombocytopenia (n = 16), idiopathic thrombocytopenic purpura (n = 10), or other hematologic (n = 15) or miscellaneous conditions (n = 10). Twelve of the 68 patients had subnormal levels of ADAMTS13 activity (相似文献
8.
Thrombotic thrombocytopenic purpura (TTP) is a syndrome characterized by microangiopathic hemolytic anemia and thrombocytopenia with varying degrees of renal dysfunction, neurologic signs and symptoms, and fever. Evidence has supported that a large proportion of cases of acquired TTP are due to the accumulation of ultralarge von Willebrand factor (vWF) multimers due to an acquired deficiency in the vWF cleaving protease, ADAMTS-13. TTP is rare in the post-surgical setting but is best described after cardiothoracic and vascular surgeries. We present a case of postoperative TTP first presenting with microangiopathic hemolytic anemia and thrombocytopenia 9 days after emergent appendectomy for a ruptured appendix. ADAMTS-13 and factor H levels returned normal and an ADAMTS-13 inhibitor was not identified. To our knowledge, this is the first case report of postoperative TTP after an appendectomy and the first report with correlative ADAMTS-13 data. Plasma exchange with fresh frozen plasma followed by cryopoor plasma, along with steroids resulted in eventual remission of TTP in our patient. Early postoperative diagnosis and aggressive management with consideration of initiation of plasma exchange is imperative to decrease the morbidity and morality associated with TTP. 相似文献
9.
Michelle A. Elliott Louis Letendre Dennis A. Gastineau Jeffrey L. Winters Rajiv K. Pruthi John A. Heit 《European journal of haematology》2010,85(1):43-50
Background: Early initiation of plasma exchange (PE) allows more than 80% of patients with idiopathic thrombotic thrombocytopenic purpura (TTP), most commonly because of severe ADAMTS13 deficiency, to achieve remission and mandates urgency in diagnosis and therapy. Metastatic cancer may present with a microangiopathic hemolytic anemia with thrombocytopenia that is clinically similar to TTP but does not respond to PE. ADAMTS13 activity can be diagnostic but usually not immediately available. Recognition of cancer‐associated microangiopathic hemolytic anemia with thrombocytopenia (CA‐MHA) is paramount to avoid inappropriate PE therapy and delays in cancer‐specific chemotherapy. Objective: To identify distinguishing characteristics of CA‐MHA and TTP to facilitate early recognition of CA‐MHA. Methods: In a retrospective cohort study, baseline clinical and laboratory data of consecutive adult patients with CA‐MHA (n = 7) or autoimmune TTP (n = 7) from a registry of patients with clinically suspected acute TTP referred for PE were compared. Results: The frequencies of bone pain and respiratory symptoms were significantly greater among patients with CA‐MHA compared to patients with TTP; other baseline clinical and laboratory characteristics did not differ significantly between the two groups. Response to PE and mortality at day 30 were significantly worse for CA‐MHA (14% and 71%, respectively) compared to patients with TTP (86% and 14%, respectively). Conclusions: Baseline clinical and laboratory characteristics largely do not distinguish acute CA‐MHA from autoimmune acute TTP. While all suspected acute patients TTP should receive urgent PE, bone pain, respiratory symptoms, or inadequate PE response should prompt an early search for CA‐MHA. 相似文献
10.
Mutations and common polymorphisms in ADAMTS13 gene responsible for von Willebrand factor-cleaving protease activity 总被引:22,自引:0,他引:22
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Kokame K Matsumoto M Soejima K Yagi H Ishizashi H Funato M Tamai H Konno M Kamide K Kawano Y Miyata T Fujimura Y 《Proceedings of the National Academy of Sciences of the United States of America》2002,99(18):11902-11907
von Willebrand factor (VWF) is synthesized primarily in vascular endothelial cells and secreted into the plasma as unusually large VWF multimers. Normally, these multimers are quickly degraded into smaller forms by a plasma metalloproteinase, VWF-cleaving protease (VWF-CP). Decreases in the activity of this enzyme result in congenital and acquired thrombotic thrombocytopenic purpura (TTP). The human VWF-CP has recently been purified. Cloning of the corresponding cDNA revealed that the 1,427-aa polypeptide is a member of the ADAMTS gene family, termed ADAMTS13. Twelve rare mutations in this gene have been identified in patients with congenital TTP. Here, we report missense and nonsense mutations in two Japanese families with Upshaw-Schulman syndrome, congenital TTP with neonatal onset and frequent relapses. The comparison of individual ADAMTS13 genotypes and plasma VWF-CP activities indicated that the R268P, Q449stop, and C508Y mutations abrogated activity of the enzyme, whereas the P475S mutant retained low but significant activity. The effects of these mutations were further confirmed by expression analysis in HeLa cells. Recombinant VWF-CP containing either the R268P or C508Y mutations was not secreted from cells. In contrast, Q449stop and P475S mutants were normally secreted but demonstrated minimal activity. Genotype analysis of 364 Japanese subjects revealed that P475S is heterozygous in 9.6% of individuals, suggesting that approximately 10% of the Japanese population possesses reduced VWF-CP activity. We report on a single-nucleotide polymorphism associated with alterations in VWF-CP activity; it will be important to assess this single-nucleotide polymorphism as a risk factor for thrombotic disorders. 相似文献
11.
Schiviz A Wuersch K Piskernik C Dietrich B Hoellriegl W Rottensteiner H Scheiflinger F Schwarz HP Muchitsch EM 《Blood》2012,119(25):6128-6135
Deficiency of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13), a VWF-cleaving protease, is the key factor in the pathogenesis of thrombotic thrombocytopenic purpura (TTP), a life-threatening thrombotic microangiopathy. It is well established that ADAMTS13 deficiency results in elevated plasma levels of ultra-large VWF multimers (ULVWF), which are prone to induce platelet aggregation; however, the actual trigger of TTP development remains uncertain. Here we describe a new animal model in which some TTP-like symptoms can be triggered in ADAMTS13 knockout mice by challenge with 2000 units/kg body weight of recombinant human VWF containing ULVWF multimers. Animals rapidly showed clinical symptoms and developed severe thrombocytopenia. Schistocytosis, a decrease in hematocrit, and elevated serum lactate dehydrogenase levels were observed. The heart was identified as the most sensitive target organ with rapid onset of extensive platelet aggregation in the ventricles and myocardial necrosis. Prophylactic administration of 200 units/kg recombinant human ADAMTS13 protected ADAMTS13 knockout mice from developing TTP. Therapeutic administration of 320 units/kg rhADAMTS13 reduced the incidence and severity of TTP findings in a treatment interval-dependent manner. We therefore consider this newly established mouse model of thrombotic microangiopathy highly predictive for investigating the efficacy of new treatments for TTP. 相似文献
12.
Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome in children and adolescents 总被引:3,自引:0,他引:3
Thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) are both uncommon disorders that present with a microangiopathic hemolytic anemia and thrombocytopenia. Although for TTP, neurologic manifestations predominate, and in HUS renal dysfunction is virtually always present, there is significant overlap in their clinical presentation. In recent years, tremendous progress has been made in our understanding of the pathogenesis of these disorders. It is now apparent that there are subcategories of both TTP and HUS that can differ in their clinical manifestations, etiology, and management. For instance, although most cases of HUS are due to infection with organisms that produce Shiga-like toxin, other cases may be caused by defined genetic abnormalities. Similarly, TTP is usually caused by genetic or acquired deficiency of the ADAMTS13 enzyme; however, in other cases the relationship with this enzyme remains to be established. Management includes supportive care, plasma transfusions for genetic protein deficiencies, and plasma exchange transfusion for autoimmune TTP. 相似文献
13.
Forastiero R 《Hematology (Amsterdam, Netherlands)》2012,17(Z1):S153-S155
Antiphospholipid syndrome (APS) is an autoimmune disease characterized clinically by the occurrence of venous or arterial thrombosis, and/or pregnancy morbidity. The detection of persistently elevated levels of antiphospholipid antibodies (aPL) is a requisite laboratory feature for the diagnosis of APS. The positivity for at least one aPL test: lupus anticoagulant and/or IgG/IgM anticardiolipin and/ or IgG/IgM anti-β2 glycoprotein I antibodies must be detected. Sometimes aPL coagulopathy may start with a hemorrhagic syndrome when a severe thrombocytopenia, or an acquired thrombocytopathy, or an acquired factor VIII inhibitor, or an acquired prothrombin deficiency is present. aPL-associated thrombocytopenia is usually moderate without clinical manifestations. Except in the occasional situations in which thrombocytopenia is associated with thrombotic microangiopathy, such as catastrophic APS, bleeding is uncommon in APS patients. When platelet counts are less than 30 × 109/L and there are symptoms of bleeding, the treatments used are the same for idiopathic thrombocytopenic purpura. In rare occasions a hemorrhagic diathesis due to the occurrence of non-neutralizing anti-prothrombin antibodies causing severe hypoprothrombinemia (HPT) can be observed. Levels of prothrombin in plasma are less than 10-20% in cases with HPT-related bleeding requiring transfusion and/or corticosteroid treatment. The APS mainly causes thrombosis, and pregnancy losses. However, other clinical manifestations are also associated with the presence of persistent autoimmune aPL. Bleeding is uncommon but can be the first clinical manifestation in patients having severe thrombocytopenia or prothrombin deficiency. 相似文献
14.
Meyer SC Jeddi R Meddeb B Gouider E Lämmle B Kremer Hovinga JA 《Annals of hematology》2008,87(8):663-666
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. 相似文献
15.
Thrombotic microangiopathies and HIV infection: Report of two typical cases, features of HUS and TTP, and review of the literature 总被引:3,自引:0,他引:3
Summary Haemolytic uraemic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) are thrombotic microangiopathies increasingly
reported in patients with HIV infection. However, characteristic features of thrombotic microangiopathies associated with
HIV disease have not been defined yet. The typical courses of HUS and TTP in two patients are presented. The data as well
as the analysis of cases published in the literature demonstrate the association of thrombotic microangiopathies with late-stage
HIV disease. Moreover, differences between HUS and TTP can be detected. Patients with HUS present with more severe immunologic
deterioration. Although clinical symptoms are fewer, HUS implicates a very poor prognosis. Life expectancy rarely exceeded
1 year after diagnosis. HUS and TTP should therefore be added to the international AIDS classification. 相似文献
16.
C. Rafat P. Coppo F. Fakhouri V. Frémeaux-Bacchi C. Loirat J. Zuber E. Rondeau 《La Revue de médecine interne / fondée ... par la Société nationale francaise de médecine interne》2017,38(12):817-824
Thrombotic microangiopathies (TMA) represent an eclectic group of conditions, which share hemolytic anemia and thrombocytopenia as a common defining basis. Remarkable breakthroughs in the physiopathological setting have allowed for a thorough recomposition of the disparate syndromes, which form the constellation of TMA. In this view, clinicians now discriminate thrombocytopenic thrombotic purpura (TTP) defined by a severe deficiency in ADAMTS13, which is rarely associated with a severe renal involvement and the hemolytic and uremic syndrome (HUS) in which renal impairment is the most prominent clinical feature. HUS can result from toxins stemming from bacterial infections of the digestive tract, alternate complement pathway abnormalities, metabolic or coagulation disorders or, lastly, drug and various toxic compounds. The diverse forms of HUS reflect the insights gained in the understanding of the pathophysiological mechanisms underpinning TMA. In this first part, a broad overview of the epidemiological, physiopathological and clinical aspects of HUS and related TMA syndromes is presented. 相似文献
17.
M U Rarick B Espina R Mocharnuk Y Trilling A M Levine 《American journal of hematology》1992,40(2):103-109
Three cases of thrombotic thrombocytopenic purpura (TTP) and coexistent human immunodeficiency virus (HIV) infection are presented with a review of 15 cases reported in the literature. Of the 18 total patients, one-half presented with no symptoms of HIV infection while nine patients presented with symptomatic HIV disease before or simultaneous to the diagnosis. The presenting symptoms were similar to those with classic TTP and included fever in 75% and 40% with neurologic symptoms. Laboratory parameters reflected the microangiopathic hemolytic anemia typically seen in patients with TTP. The median hematocrit was 19.4%, while the median platelet count was 16,000/mm3. As with classic TTP, patients with HIV-related TTP only had mild renal dysfunction (median creatinine of 1.2 mg/dl, range 0.8-4.8 mg/dl). Plasma exchange produced clinical remission in a majority of the patients. Importantly, approximately one-third of the patients died prior to the initiation of therapy. We conclude that TTP is a rare but treatable condition in patients with HIV infection. A TTP diagnosis should be considered in patients with HIV infection who present with severe anemia and thrombocytopenia. Plasma exchange should be considered as initial therapy. The role of both antiplatelet therapy and aspirin is unknown. 相似文献
18.
T L Ellingson K Wilske D M Aboulafia 《The American journal of the medical sciences》1992,303(6):407-410
Thrombotic thrombocytopenic purpura (TTP) is characterized by the pentad of fever, thrombocytopenia, microangiopathic hemolytic anemia, fluctuating neurologic symptoms, and renal dysfunction. Thrombotic thrombocytopenic purpura has recently been reported in association with rheumatic diseases (RDs). The authors present a patient with TTP and polymyositis and speculate on the pathophysiology linking these two conditions. Thrombotic thrombocytopenic purpura and RDs may present with overlapping clinical and laboratory features. It is important to identify TTP as a cause of thrombocytopenia and hemolysis when occurring in patients with RDs since management, treatment, and prognosis differ. Early recognition and prompt institution of plasmapheresis may improve the outcome in patients with TTP. 相似文献
19.
Patients with malignant hypertension sometimes exhibit microangiopathic hemolytic anemia/thrombocytopenia known as thrombotic microangiopathy (TMA). On the other hand, severe hypertension is sometimes associated with hemolytic uremic syndrome (HUS)/thrombotic thrombocytopenic purpura (TTP). Because the clinical features of the two entities overlap significantly, it is sometimes difficult to distinguish one from the other. However, such differentiation is indispensable, since early performance of plasmapheresis is critical in HUS/TTP. It has been suggested that severe thrombocytopenia is one of the most useful differential points in diagnosing HUS/TTP from malignant hypertension caused by other etiologies. Early performance of plasmapheresis can be justified in the presence of both TMA and thrombocytopenia. However, thrombocytopenia can be seen in the cases with malignant hypertension from etiologies other than HUS/TTP, and in these particular cases, plasmapheresis is useless and can be harmful. Recently, the plasma level of ADAMTS13 (a disintegrin and metalloprotease domain, with thrombospondin type 1 motif 13), which is a von Willebrand Factor cleaving protease, has been shown to be very low in familial or some of the sporadic cases of TTP, and a low level of ADAMTS13 is very specific to TTP. Some reports have shown that patients with a very low plasma level of ADAMTS13 respond very well to plasmapheresis. We recently experienced two cases with TMA. Although both of our patients had severe hypertension with TMA, different therapeutic strategies ameliorated their illness: symptomatic treatment was effective in case 1, which showed normal ADAMTS13 activity, whereas plasma infusion was necessary to save case 2, which showed low ADAMTS13 activity. Thus, patients with a low level of ADAMTS13 activity might respond well to plasmapheresis or plasma infusion. When presented with patients with severe hypertension and thrombotic microangiopathy, ADAMTS13 activity may prove to be a promising adjunctive tool in differentiating TTP from TMA due to other etiologies, but in the meantime, we should make the choice of whether or not to perform plasmapheresis based on the degree of thrombocytopenia. 相似文献
20.
Ishikawa T Makita M Saeki K Hara Y Yamamoto K Imajo K 《[Rinshō ketsueki] The Japanese journal of clinical hematology》2012,53(6):628-631
Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease that is a rare complication of thienopyridine treatment, especially clopidogrel. Here we report a case of clopidogrel-associated TTP. A 77-year-old male initially complained of petechiae on his legs 6 weeks after clopidogrel treatment following coronary artery stenting. He was admitted 4 weeks later with slurred speech and low-grade fever. Laboratory findings showed severe thrombocytopenia, hemolytic anemia with fragmented red cells, renal dysfunction and severe deficiency of ADAMTS13 activity with the presence of the inhibitor. Based on the clinical course and laboratory findings, he was diagnosed with TTP and underwent plasma exchange, followed by improvement of symptoms and laboratory abnormalities after 7 courses of plasma exchange. Nevertheless, the patient died of sepsis due to perforated small intestinal diverticulitis 89 days after admission. Thienopyridine-associated TTP usually occurs within 12 weeks after initiation of the therapy. Physicians should therefore be aware of this fatal complication associated with clopidogrel therapy and frequent blood tests, every 2 weeks during the first 12 weeks, is recommended for early diagnosis. 相似文献