Thrombotic microangiopathy tma lesions could present with normal plt and lead to substantial renal damage quite commonly. Etiology and outcomes of thrombotic microangiopathies. Abstract neurological manifestation of thrombotic microangiopathy tma after renal transplantation is rare and. With the identification of etiologic roles for factor h in hus and for adamts in ttp, these are now thought to be distinct disorders with overlapping clinical features. The differential diagnosis of thrombotic microangiopathy tma is complex however the rapid diagnosis of the underlying condition is vital to inform urgent treatment decisions.
Review renal thrombotic microangiopathy in patients with cblc defect. Thrombotic microangiopathy associated with synthetic. In this abstract, we describe two young patients who lived together and used opana er intravenously. Thrombotic thrombocytopenic purpura ttp is a blood disorder that results in blood clots forming in small blood vessels throughout the body. Abstract neurological manifestation of thrombotic microangiopathy tma after renal transplantation is rare and dif cult to be distinguished from other conditions. A survey was devised with the objective of understanding current practices across europe and the middle east, and of challenges when diagnosing the cause of tma. Congenital ttp is a rare autosomal recessive disease present in childhood. Drug induced thrombotic microangiopathy caused by levofloxacin. Thrombotic microangiopathy tma is a pathology that results in thrombosis in capillaries and arterioles, due to an endothelial injury.
Definition lesion of arterioles and capillaries with wall thickening, intraluminal platelet thrombosis and partial or complete obstruction of vessel lumina. Thrombotic microangiopathy associated with monoclonal. The peripheral blood smear showed manifold schistocytes 2. The lesion consists of fibrin thrombi within glomeruli, which may extend to arterioles. Thrombotic microangiopathy an overview sciencedirect topics. Renal thrombotic microangiopathy and podocytopathy. Thrombotic microangiopathy in a patient treated with. Diagnosis can be difficult, as there is clinical overlap with haemolytic uraemic syndrome hus, autoimmune disease and a spectrum of pregnancy. Thrombotic microangiopathy tma syndromes are defined clinically by microangiopathic hemolytic anemia, thrombocytopenia, organ injury, and arteriolar and capillary thrombosis. Thrombotic microangiopathy with atypical posterior. Thrombotic microangiopathy and associated renal disorders.
Among various lupus renal vascular changes, thrombotic microangiopathy tma presented with the. Kidney biopsy was not performed in any of these cases. Thrombotic microangiopathy tma after renal transplantation is a rare but serious complication. Thrombotic microangiopathy often known simply as tma is a rare but serious medical disease. The conundrum of postpartum thrombotic microangiopathy.
Thrombotic thrombocytopenia purpura ttp is a disseminated thrombotic microangiopathy that can be triggered by infection, drugs e. Thrombotic thrombocytopenic purpura ttp, a thrombotic microangiopathy tma, is a syndrome consisting of microangiopathic hemolytic anemia maha, thrombocytopenia, and endorgan damage secondary to microvascular thrombi. Thrombotic microangiopathy is a pathology that results in thrombosis in capillaries and arterioles, due to an endothelial injury. It is a pattern of damage that can occur in the smallest blood vessels inside many of your bodys vital organs most commonly the kidney and brain. The thrombotic microangiopathies are microvascular occlusive disorders characterized by systemic or intrarenal aggregation of platelets, thrombocytopenia, and mechanical injury to erythrocytes. Thrombotic microangiopathy syndromes consist of a collection of disorders with a varied etiology that share common clinical and pathological features. Thrombotic microangiopathic diseases thrombotic thrombocytopenic purpura ttp is categorized into acquired idiopathic ttp and congenital familial ttp. Thrombotic microangiopathy is a group of disorders that is characterized by thrombocytopenia and microangiopathic hemolytic anemia intravascular hemolysis and presence of peripheral blood schistocytes, neurological symptoms, fever, and renal dysfunction. Diseases linked by endothelial injury leading to aggregation of platelets on the damaged endothelium in capillaries and arterioles with microvascular thrombosis and organ dysfunction related to microvascular injury shiga toxinproducing e. Thrombotic microangiopathy tma in atypical hemolytic uremic syndrome ahus versus thrombotic thrombocytopenia purpura ttp tma is a general category consisting of abnormal deposition of thrombi in microvesciles throughout the body and is associated with many disorders. The two basic clinical forms of thrombotic microangiopathy excluding disseminated intravascular coagulation dic, thrombotic thrombocytopenic purpura ttp, and hemolytic uremic syndrome hus encompass a wide range of primary and secondary forms. Thrombotic microangiopathy associated with monoclonal gammopathy.
In addition to ttp and hus, tma may occur in other disorders, such as. Opana er oxymorphone is an opioid drug available throughout the united states, and intravenous abuse of the crushed oral formulation has been associated with druginduced thrombotic microangiopathy. Thrombotic microangiopathy tma is a rare, potentially lifethreatening condition comprising a diverse set of disorders including hemolytic uremic syndrome hus, complementmediated tma also known as atypical hus ahus, thrombotic thrombocytopenic purpura ttp, coagulationmediated tma, metabolic disordermediated tma, and other associated conditions. Pttm is a fatal, cancerrelated pulmonary complication, characterized by progressive dyspnoea, pulmonary hypertension and rightsided heart failure. Definition of thrombotic microangiopathy in the dictionary. Causes of tma include thrombotic thrombocytopenia purpura ttp, haemolytic uraemic syndrome. Acquired thrombotic thrombocytopenic purpura ttp and hemolytic uremic syndrome hus are appropriately at the top of a. Fervenza2 and sanjeev sethi3 1division of hematology, mayo clinic, rochester, minnesota, usa. Thrombotic microangiopathy tma is characterized by the presence of microangiopathic hemolytic anemia and thrombocytopenia along with organ dysfunction, and pathologically, by the presence of microthrombi in multiple microvascular beds.
Paroxysmal nocturnal hemoglobinuria pnh is a rare clonal hematopoietic stem cell disorder clinically characterized by chronic complementmediated hemolysis, thrombosis, and impaired hematopoiesis. Thrombotic microangiopathy in a patient treated with gemcitabine. Druginduced thrombotic microangiopathy due to cumulative toxicity of ixazomib druginduced thrombotic microangiopathy due to cumulative toxicity of ixazomib. Profound thrombocytopenia and microangiopathic hemolytic anemia characterize thrombotic microangiopathy, which includes two major disorders. It is an unusual and recognized complication of chemotherapy. Thrombotic microangiopathy tma is an ultrarare syndrome. We describe herein the case of a patient with lung adenocarcinoma who developed. Despite the extensive use of sunitinib in patients with renal cell carcinoma and other malignancies. It is a group of disor ders characterized by microangiopathic hemo. Oct 28, 2017 the differential diagnosis of thrombotic microangiopathy tma is complex however the rapid diagnosis of the underlying condition is vital to inform urgent treatment decisions.
Thrombotic microangiopathy with atypical posterior reversible encephalopathy syndrome pres after kidney transplantation. Thrombotic thrombocytopenic purpura ttp and hemolytic uremic syndrome hus are two prototypes of tmas, although tmas may occur secondarily to multiple other systemic disorders eg, malignant hypertension, medications. Other conditions with tma include atypical hemolytic uremic syndrome, disseminated intravascular. Anemia, thrombocytopenia, fever, neurological signs and renal abnormalities make up the classic pentad. Diseases linked by endothelial injury leading to aggregation of platelets on the damaged endothelium in capillaries and arterioles with microvascular thrombosis. Historically, hus and ttp were considered to be variable expressions of the same disease process. Thrombotic microangiopathy tma manifests as a histological lesion of the microvasculature characterised by thickened and swollen vessel walls, detachment of endothelial cells, buildup of proteins and cell lysis material in the subendothelial space, and. May 05, 2017 thrombotic microangiopathy associated with synthetic cannabinoid receptor agonists marijuana is one of the most commonly used recreational drugs in the united states.
Thrombotic microangiopathy is a lesion seen in many conditions, including hemolytic uremic syndrome, radiation nephritis, toxicity related to various drugs, and hereditary forms. Thus, the exclusion of other primary tma syndromes may not be possible. Guidelines on the diagnosis and management of thrombotic. Pdf etiology and outcomes of thrombotic microangiopathies. It is a process of red blood cell destruction within the. Case report use of cabozantinib in a lung adenocarcinoma. Atypical hemolytic uremic syndrome ahus hematology. Chronic thrombotic microangiopathy associated with antineoplastic therapy with minimal hematologic effects. There have been four cases of btzassociated aki with evidence of underlying tma table 1.
Pulmonary tumor thrombotic microangiopathy pttm is a fatal disease process in which pulmonary hypertension ph develops in the setting of malignancy. The classification of thrombotic microangiopathy has evolved and expanded due to treatment and mechanistic advances. The syndrome is due to deficiency of the adamts protein. Thrombosis is the major cause of death in pnh and is observed in approximately 40% of patients. Acquired ttp is mainly idiopathic, but there are other conditions and comorbidities besides idiopathic. Thrombotic thrombocytopenic purpura, acquired genetic and. Differential diagnosis of thrombotic microangiopathy in. Pdf the thrombotic microangiopathies tma are a group of diseases associated with microangiopathic hemolytic anemia, thrombocytopenia, and endorgan. This video highlights the great work being done at the unc kidney center, and features several faculty, staff, and patients. Multiple causes of thrombotic microangiopathies were more frequent in secondary than primary thrombotic microangiopathies 57% versus 19%. The differential diagnosis and treatment of thrombotic.
Thrombotic microangiopathy tma is a pathological process involving thrombocytopenia, microangiopathic haemolytic anaemia and microvascular occlusion. Thrombotic microangiopathy cases in emicizumab clinical trials, expanded access, compassionate use, and after fda approval. Acquired thrombotic thrombocytopenic purpura ttp and hemolytic uremic syndrome hus are appropriately at the top of a clinicians differential when a patient presents with a clinical picture consistent with an acute thrombotic microangiopathy tma. Thrombotic microangiopathy comprises a heterogeneous group of disorders characterized by injured endothelial cells that are thickened, swollen, or detached, mainly from arterioles and capillaries. If you do not see its contents the file may be temporarily unavailable at the journal website or you do not have a pdf plugin installed and enabled in. Thrombotic microangiopathy secondary to intravenous abuse of. Thrombotic thrombocytopenic purpura ttp and hemolytic uremic syndrome hus are two prototypes of tmas, although tmas may occur secondarily to multiple other systemic disorders eg. Jul 25, 2012 pregnancyassociated thrombotic microangiopathy is a rare but serious disorder that is associated with significant maternal and perinatal morbidity and mortality, due to the deposition of fibrin and platelet thrombi in the microcirculation of the placenta. Sunitinibinduced thrombotic microangiopathy tma is a secondary tma caused by sunitinib. Pulmonary tumour thrombotic microangiopathy pttm is a rare complication of cancer, which can be lethal due to progressive pulmonary hypertension ph. Research article open access the spectrum of renal thrombotic microangiopathy in lupus nephritis di song1, lihua wu1,2, fengmei wang1, xiaowei yang1, di zhu1, min chen1, feng yu1, gang liu1 and minghui zhao1 abstract introduction.
Thrombotic microangiopathy secondary to intravenous abuse. It may be seen in association with thrombocytopenia, anemia, purpura and kidney failure. Sri ranga bonam, sirisha chalasani, sashidhar bollini, robert grunberg, richard snyder the thrombotic microangiopathies tma share a common pathway of vascular endothelial injury and thrombus formation. Thrombotic microangiopathy with atypical posterior reversible. Very importantly, tma belongs to the thrombocytopenia. Thrombotic microangiopathy associated with proteasome inhibitors. Dec 16, 2016 thrombotic thrombocytopenic purpura, acquired acquired ttp is diagnosed by medical history, a thorough physical exam, and blood tests. Delays in diagnosis and initiation of therapy are common due to the low incidence, variable presentation, and poor awareness of these diseases.
The purpose of this study is to present a detailed analysis of cases of pttm reported in literature in the hopes of achieving more antemortem diagnoses. Thrombotic microangiopathy as a cause of cardiovascular toxicity from the bcrabl1 tyrosine kinase inhibitor ponatinib. Introduction pulmonary tumour thrombotic microangiopathy pttm is a rare complication of metastatic cancer, with a prevalence of. Thrombotic microangiopathy research papers academia. Microangiopathy literally translates to small blood vessel problem. Research article open access the spectrum of renal. Thrombotic microangiopathies constitute a diagnostic and therapeutic challenge. Kdigo controversies conference on complementmediated kidney diseases november 1921. Although thrombotic microangiopathy is rare, it is as sociated with significant morbidity and mortality. Thrombotic microangiopathies tma are clinical syndromes defined by the presence of hemolytic anemia destruction of red blood cells, low platelets, and organ damage due to the formation of microscopic blood clots in capillaries and small arteries.
Thrombotic thrombocytopenic purpura after allogeneic stem cell transplantation. Without early recognition and intervention, the prognosis of the disease is poor. Syndromes of thrombotic microangiopathy n engl j med 371. We had considered this because studies frequently describe pneumococcal sepsismediated throm botic microangiopathy.
Case report, cabozantinib, thrombotic microangiopathy, angiotensinconverting enzyme inhibitor introduction thrombotic microangiopathy tma was first introduced by symmers in 1952 as the shortened version for thrombotic microangiopathic haemolytic anaemia 1, 2. Thrombotic thrombocytopenic purpura ttp is a thrombotic microangiopathy tma characterized by plateletrich microthrombi which occlude capillaries and result in thrombocytopenia, hemolytic. Pdf the thrombotic microangiopathies tma are a group of diseases associated with microangiopathic hemolytic anemia, thrombocytopenia, and end organ. Medical history suggestive of ttp might include having had certain diseases or conditions, such as cancer, hiv, lupus, or recent infections or recent pregnancy, all of which can be triggers for the onset of ttp. Campistol, nephrology and renal transplant department, hospital clinic, university of barcelona, barcelona, spain. Several case reports have demonstrated that imatinib, a plateletderived growth factor receptortyrosine kinase inhibitor, can improve severe ph in patients with pttm. Pdf understanding thrombotic microangiopathies in children. Ischemic organ injury can occur to the brain, kidneys, heart. As marijuana is illegal in the majority of countries, the use of readily available and unregulated synthetic cannabinoids scbs has increased.
Athrombocytopenic thrombotic microangiopathy 30 yr retrospective cohort who underwent kidney biopsies before 2007 and were found to have intimal proliferaton andor endothelial swelling with luminal fibrin deposition in arterial or capillary beds but no signs of vasculitis, acute rejections or extensive microthrombosis. The classic tmas are hemolytic uremic syndrome and thrombotic thrombocytopenic purpura. The morphological lesions in these various conditions are the same. These observations raise the concern that athrombocytopenic tma may not be considered for timely therapeutic interventions based on current diagnostic criteria or because of. This results in a low platelet count, low red blood cells due to their breakdown, and often kidneys, heart, and brain dysfunction. Renal thrombotic microangiopathy in patients with cblc defect. However, we did not include it in our set of primary syndromes because of the limited mechanistic evidence that it is a. Thrombotic microangiopathy associated with proteasome. Over 450 clinicians, from 16 countries were invited to. Thrombotic microangiopathy tma syndromes can be acquired or hereditary. The kidneys are commonly affected, although virtually any organ may be involved. Symptoms may include large bruises, fever, weakness, shortness of breath, confusion, and headache. Other clinical forms of thrombotic microangiopathy tma occur in the absence of severe deficiency.
Hematopoietic transplantassociated thrombotic microangiopathy. Microangiopathic hemolytic anemia is the hallmark of thrombotic microangiopathy. Renal thrombotic microangiopathy in patients with cblc. Syndromes of thrombotic microangiopathy tma, defined by microangiopathic hemolytic anemia, thrombocytopenia, and microvascular thrombosis with characteristic vessel wall abnormalities, have multiple etiologies. It aired at the 2018 american society of nephrology conference, and you can check it out on youtube. Thrombotic microangiopathy tma is characterized pathologically by occlusive microvascular thrombosis and clinically by profound thrombocytopenia, microangiopathic hemolytic anemia, and variable signs and symptoms of organ ischemia.