Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A four-year old boy was admitted to the hospital due to acute thrombocytopenic purpura. Three days later he developed edema, hematuria and hypertension. The diagnosis of acute poststreptococcal glomerulonephritis was based upon the evidence of previous sore throat, hypocomplementemia and increased antistreptolysin O titer. Renal biopsy was contraindicated due to throbocytopenia. An extensive work-up was done to exclude mebranoproliferative glomerulonephritis and systemic diseases such as hemolytic uremic syndrome or systemic lupus erythematosus. The clinical outcome of the nephritis and thrombocytopenia was excellent in respect to both conditions. To the best of our knowledge concurrent occurrence of acute thrombocytopenic purpura and poststreptococcal glomerulonephritis is very rare; there are only four similar cases reported in the literature. A careful work-up and follow-up are mandatory to exclude systemic disease.
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PMID:Thrombocytopenia during the course of acute poststreptococcal glomerulonephritis. 1292 3

Systematic evaluations of anemia, thrombocytopenia, and coagulopathy are essential to identifying and managing their causes successfully. In all cases, clinicians should evaluate RBC measurements alongside WBC and platelet counts and WBC differentials. Multiple competing factors may coexist; certain factors affect RBCs independent of those that affect WBCs or platelets. Ideally, clinicians should examine the peripheral blood smear for morphologic features of RBCs, WBCs, and platelets that provide important clues to the cause of the patient's hematologic disorder. Thrombocytopenia arises from decreased platelet production, increased platelet destruction, or dilutional or distributional causes. Drug-induced thrombocytopenias present diagnostic challenges, because many medicines can cause thrombocytopenia and critically ill patients often receive multiple medications. If they suspect type II HIT, clinicians must promptly discontinue all heparin sources, including LMWHs, without awaiting laboratory confirmation, to avoid thrombotic sequelae. Because warfarin anticoagulation induces acquired protein C deficiency, thereby exacerbating the prothrombotic state of type II HIT, warfarin should be withheld until platelet counts increase to more than 100,000/microL and type II HIT is clearly resolving. The presence of a consumptive coagulopathy in the setting of thrombocytopenia supports a diagnosis of DIC, not TTP-HUS, and is demonstrated by decreasing serum fibrinogen levels, and increasing TTs, PTs, aPTTs, and fibrin degradation products. Increasing D-dimer, levels are the most specific DIC parameter and reflect fibrinolysis of cross-linked fibrin. Elevated PTs or a PTTs can result from the absence of factors or the presence of inhibitors. Clinicians should suspect factor inhibitors when the prolonged PT or aPTT does not correct or only partially corrects following an immediate assay of a 1:1 mix of patient and normal plasma. In addition to factor inhibitors, antiphospholipid antibodies (e.g., lupus anticoagulant) can produce a prolonged aPTT that does not correct with normal plasma but is overcome by adding excess phospholipid or platelets. Paradoxically, a tendency to thrombosis, not bleeding, accompanies lupus anticoagulants and the antiphospholipid antibody syndrome. Transfusion of red blood cells, platelets, or plasma products is sometimes warranted, but clinicians must carefully weigh potential benefits against known risks. In critically ill patients, administering RBCs can enhance oxygen delivery to tissues. Among euvolemic patients who do not have ischemic heart disease, guidelines recommend a transfusion threshold of HGB levels in the range of 6.0 to 8.0 g/dL; patients who have HGB that is at least 10.0 g/dL are unlikely to benefit from blood transfusion. The use of rHuEPO to increase erythropoiesis offers an alternative to RBC transfusion, assuming normal, responsive progenitor cells and adequate iron, folate, and cobalamin stores. Future research should examine whether clinical outcomes from rHuEPO use in critically ill patients are important and cost-effective. Because platelets play an instrumental role in primary hemostasis, platelet transfusions are often important in managing patients who are bleeding or at risk of bleeding with thrombocytopenia or impaired platelet function. Platelet transfusions carry risks, and decisions to transfuse platelets must consider clinical circumstances. Most important, platelet transfusions are generally contraindicated if the underlying disorder is TTP or type II HIT, because platelet transfusion in these settings may fuel thrombosis and worsen clinical signs and symptoms. Plasma products can correct hemostasis when bleeding arises from malfunction, consumption, or underproduction of plasma coagulation proteins. Choice of plasma product for transfusion depends on clinical circumstances. FFP is the most commonly used plasma product to correct clotting factor deficiencies, particularly coagulopathies that are attributable to multiple clotting factor deficiency states as in liver disease, DIC, or warfarin anticoagulation. PCC or rFVIIa that is administered in small volumes may provide advantages over FFP when coagulopathies require quick reversal without risk of volume overload. Factor concentrates can replace specific factor deficiencies. Recombinant FVIIa bypasses inhibitors to factors VIII and IX and vWF. Use of rFVIIa in managing hemostatic abnormalities from severe liver dysfunction; extensive surgery, trauma, or bleeding; excessive warfarin anticoagulation; and certain platelet disorders requires further study to determine optimal and cost-effective dosing regimens. Recombinant activated protein C reduces mortality from severe sepsis that is associated with organ dysfunction in adults who are at high risk for death (APACHE scores of at least 25). In severe sepsis, levels of protein C decrease, as do fibrinogen and platelet levels. Because of its anticoagulant effect, however, drotrecogin alfa may induce bleeding. Guidelines for drotrecogin alfa use must take into account bleeding risks.
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PMID:Critical issues in hematology: anemia, thrombocytopenia, coagulopathy, and blood product transfusions in critically ill patients. 1471 Jun 93

Associating systemic lupus erythematosus (SLE), with an initial presentation of hemolytic uremic syndrome (HUS) is rare. We report a case of 21-year old Afghani female admitted to our hospital with an initial complaint of high grade fever and diffuse maculopapular rash and swelling of lower limbs. Diagnosis of atypical HUS was established according to the clinical triad of HUS without a veriotoxin-producing organism in her stool and the pathological finding compatible to thrombotic microangiopathy. In addition, her symptoms fulfilled the 1982 revised criteria for the classification of SLE. After pulse methylprednisolone, cyclophosphamide and plasmapheresis therapies, her laboratory findings and general condition improved. Unfortunately she was lost to follow up as she decided to return back to Afghanistan.
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PMID:Systemic lupus erythematosus presenting as hemolytic uremic syndrome: a case report. 1581 38

Hemolytic uremic syndrome (HUS) as an initial presentation of systemic lupus erythematosus (SLE) is a rare finding. We report a 25-year-old female patient who presented to our hospital with complaint of fever, joint pain, anasarca, hematuria and nose bleed. Her diagnostic workup revealed renal failure, microangiopathic hemolytic anemia and thrombocytopenia due to SLE with HUS. The patient initially responded well to treatment with steroids, plasmapheresis with cryosupernatant and cyclophosphamide but finally succumbed to enterococcus septicemia.
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PMID:Hemolytic uremic syndrome with systemic lupus erythematosus. 1590 46

Hemolytic uremic syndrome (HUS) includes a heterogeneous group of hemolytic disorders. Among the identified causes of HUS are infections, particularly infections with Shiga toxin-producing ESCHERICHIA COLI (STEC), complement disorders, and disorders interfering with the degradation of von Willebrand factor (VWF). Other causes for atypical HUS include the cobalamin metabolism; pregnancy/hemolysis, elevated liver enzymes, and low platelets syndrome (HELLP); drugs; and other disorders (e.g., systemic diseases appearing as HUS, such as systemic lupus erythematosus and rejection after transplantation). The group not related to STEC is often also called atypical HUS. Most of the occurrences of infectious HUS have only one episode. Recurrent episodes (recurrent HUS) have strong relationships to diseases of the complement system. In these two subgroups the prognosis is poor, with severe renal insufficiency, together with the need for renal replacement therapy. Severe arterial hypertension is common. Treatment options are limited. To better define this group of patients, the European Society for Pediatric Nephrology supported an initiative to develop a European HUS registry. In this registry, 167 patients were acquired; 73 were female (43.8%). The year of onset of the disease ranged from 1974 to 2005. The prevalence of atypical HUS/recurrent HUS can be calculated as 3.3 per million child population (< 18 years). Underlying disorders included factor H, factor I, MCP-1, pneumococci, and von Willebrand factor disturbances. In 33 patients at least one renal transplantation was performed (total, 55 kidneys); 18% were successful and 73% demonstrated recurrence or thrombosis. Treatment options were plasma substitution or plasmapheresis. Despite continued efforts, transplantation is not recommended at present for these patients. Living-related transplantation should be abandoned. New therapeutic strategies are urgently needed.
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PMID:Epidemiology, clinical presentation, and pathophysiology of atypical and recurrent hemolytic uremic syndrome. 1657 86

Haemolytic uraemic syndrome (HUS) is the most common cause of acute renal failure in children. The syndrome is defined by triad of microangiopathic haemolytic anaemia, thrombocytopenia and acute renal failure (ARF). Incomplete HUS is ARF with either haemolytic anaemia or thrombocytopenia. HUS is classified into two subgroups. Typical HUS usually occurs after a prodrome of diarrhoea (D+HUS), and atypical (sporadic) HUS (aHUS), which is not associated with diarrhoea (D-HUS). The majority of D+HUS worldwide is caused by Shiga toxin-producing Esherichia coli (STEC), type O157:H7, transmitted to humans via different vehicles. Currently there are no specific therapies preventing or ameliorating the disease course. Although there are new therapeutic modalities in the horizon for D+HUS, present recommended therapy is merely symptomatic. Parenteral volume expansion may counteract the effect of thrombotic process before development of HUS and attenuate renal injury. Use of antibiotics, antimotility agents, narcotics and non-steroidal anti-inflammatory drugs should be avoided during the acute phase. Prevention is best done by preventing primary STEC infection. Underlying aetiology in many cases of aHUS is unknown. A significant number may result from underlying infectious diseases, namely Streptococcus pneumoniae and human immunedeficiency virus. Variety of genetic forms include HUS due to deficiencies of factor H, membrane cofactor protein, Von Willebrand factor-cleaving protease (ADAMTS 13) and intracellular defect in vitamin B12 metabolism. There are cases of aHUS with autosomal recessive and dominant modes of inheritance. Drug-induced aHUS in post-transplantation is due to calcineurin-inhibitors. Systemic lupus erythematosus and catastrophic antiphospholipid syndrome may also present with aHUS. Therapy is directed mainly towards underlying cause.
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PMID:Haemolytic uraemic syndrome: an overview. 1675 34

Thrombotic microangiopathy, which includes thrombotic thrombocytopenic purpura (TTP), shiga-toxin-associated hemolytic uremic syndrome (Stx-HUS) and atypical HUS, is characterized by the development of hyaline thrombi in the microvasculature resulting in thrombocytopenia, microangiopathic hemolysis, and organ dysfunction. Renal failure is a predominant complication of both Stx-HUS and atypical HUS, whereas neurological complications are more prominent in TTP. Other disorders such as lupus or bone marrow transplantations may occasionally present with features of thrombotic microangiopathy. Recent studies have found autoimmune inhibitors or genetic mutations of a von Willebrand factor (VWF) cleaving metalloprotease ADAMTS13 in patients with TTP. In approximately 30-50% of patients with atypical HUS, mutations have been detected in complement factor H, membrane cofactor protein (CD46), or factor I. All three proteins are involved in the regulation of complement activation. Additionally, autoantibodies of factor H have been described in patients without genetic mutations. These advances illustrate that dysregulation of VWF homeostasis or complement activation owing to genetic or autoimmune mechanisms may lead to the syndrome of thrombotic microangiopathy.
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PMID:The molecular biology of thrombotic microangiopathy. 1676 Sep 11

The complement system consists of more than 30 proteins and has 3 types of activation pathways: classical, lectin and alternative pathways. The complement system not only has a role in innate immunity but also works as an antibody-dependent effecter to eliminate pathogens. It is useful to measure serum levels of CH50, C3 and C4 in patients with immune-mediated diseases. While increased levels of CH50 are associated with non-specific inflammation, decreased levels of CH50 in combination with normal or decreased levels of C3 and C4 are associated with specific immune-mediated diseases. Recent studies have demonstrated that the defect in the clearance of immune complexes and apoptotic cells is associated with autoimmune disease. Mice deficient in Clq show a lupus-like phenotype with the appearance of antinuclear antibodies and glomerulonephritis due to a defect in the clearance of immune complexes and apoptotic cells. This at least explains the paradox that, in humans, deficiency in an early complement component is a major risk factor for SLE. It is demonstrated that mutations in factor H, membrane cofactor protein (MCP) and factor I gene are associated with atypical hemolytic uremic syndrome. Since the complement system is a central mediator of inflammation, it is recognized as a promising therapeutic target. Anti-C5 monoclonal antibody was developed to block the final stage of complement activation. Pexelizumab is a single chain, short-acting anti-C5 antibody and is used for reperfusion after myocardial infarction, or for coronary artery bypass graft surgery with cardiopulmonary bypass. Eculizumab is a long-acting anti-C5 antibody used for paroxysmal nocturnal hemoglobinuria, rheumatoid arthritis, membranous glomerulonephritis with promising results.
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PMID:[Clinical aspects of the complement system]. 1691 67

There are several obstetric, medical, and surgical disorders that share many of the clinical and laboratory findings of patients with severe preeclampsia-hemolysis, elevated liver enzymes, and low platelets syndrome. Imitators of severe preeclampsia-hemolysis, elevated liver enzymes, and low platelets syndrome are life-threatening emergencies that can develop during pregnancy or in the postpartum period. These conditions are associated with high maternal mortality, and survivors may face long-term sequelae. Perinatal mortality and morbidity also remain high in many of these conditions. The pathophysiologic abnormalities in many of these disorders include thrombotic microangiopathy, thrombocytopenia, and hemolytic anemia. Some of these disorders include acute fatty liver of pregnancy, thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, and acute exacerbation of systemic lupus erythematosus. Because of the rarity of these conditions during pregnancy and postpartum, the available literature includes only case reports and case series describing these syndromes. Consequently, there are no systematic reviews or randomized trials on these subjects. Differential diagnosis may be difficult due to the overlap of several clinical and laboratory findings of these syndromes. It is important that the clinician make the accurate diagnosis when possible because the management and complications from these syndromes may be different. For example, severe preeclampsia and acute fatty liver of pregnancy are treated by delivery, whereas it is possible to continue pregnancy in those with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome and exacerbation of systemic lupus erythematosus. This review focuses on diagnosis, management, and counseling of women who develop these syndromes based on results of recent studies.
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PMID:Imitators of severe preeclampsia. 1740 Aug 60

The diagnosis of antiphospholipid syndrome (APS) relies on clinical and laboratory criteria, which have been recently outlined in specific consensus conferences. Renal involvement in APS is not infrequent and includes different clinical patterns. For clinical purposes a distinction can be made between large vessel and microvascular involvement. Renal artery stenosis is frequent in APS. In case of microvascular involvement with an acute clinical course a differential diagnosis with other thrombotic microangiopathic diseases has to be made, taking in account thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, malignant hypertension, drug nephrotoxicity (cyclosporin) and others. The disease is often chronic, with hypertension, different degrees of renal insufficiency and mild proteinuria. In patients with systemic lupus erythematosus and antiphospholipid antibodies the prognosis of kidney disease is generally poorer than in lupus alone. Finally, the kidney is almost invariably a target in catastrophic antiphospholipid syndrome. Anticoagulation is the therapy of choice, especially in arterial stenosis and acute disease, but is probably also indicated in chronic and subacute patterns. The role of immunomodulatory therapy has to be assessed.
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PMID:[Antiphospholipid syndrome and kidney]. 1745 26


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