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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acquired abnormalities in platelets, endothelium, and their interaction occur in sepsis, immune heparin-induced thrombocytopenia (HIT), and the antiphospholipid syndrome. Although of distinct pathogeneses, these three disorders have several clinical features in common, including thrombocytopenia and the potential for life- and limb-threatening thrombotic events, ranging from microvascular (sepsis > antiphospholipid > HIT) to macrovascular (HIT > antiphospholipid > sepsis) thrombosis, both venous and arterial. In Section I, Dr. William Aird reviews basic aspects of endothelial-platelet interactions as a springboard to considering the common problem of thrombocytopenia (and its mechanism) in sepsis. The relationship between thrombocytopenia and other aspects of the host response in sepsis, including activation of coagulation/inflammation pathways and the development of organ dysfunction, is discussed. Practical issues of platelet count triggers and targeted use of activated protein C concentrates are reviewed. In Section II, Dr. Theodore Warkentin describes HIT as a clinicopathologic syndrome, i.e., the diagnosis should be based on the concurrence of an appropriate clinical picture together with detection of platelet-activating and/or platelet factor 4-dependent antibodies (usually in high levels). HIT is a profound prothrombotic state (odds ratio for thrombosis, 20-40), and the risk for thrombosis persists for a time even when heparin is stopped. Thus, pharmacologic control of thrombin (or its generation), and postponing oral anticoagulation pending substantial resolution of thrombocytopenia, is appropriate. Indeed, coumarin-associated protein C depletion during uncontrolled thrombin generation of HIT can explain limb loss (coumarin-associated venous limb gangrene) or skin necrosis syndromes in some patients. In Section III, Dr. Jacob Rand presents the most recent concepts on the mechanisms of thrombosis in the antiphospholipid syndrome, and focuses on the role of beta(2)-glycoprotein I as a major antigenic target in this condition. Diagnosis of the syndrome is often complicated because the clinical laboratory tests to identify this condition have been empirically derived. Dr. Rand addresses the practical aspects of current testing for the syndrome and current recommendations for treating patients with thrombosis and with spontaneous pregnancy losses.
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PMID:Platelet-endothelial interactions: sepsis, HIT, and antiphospholipid syndrome. 1463 96

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

Purpura fulminans (PF) is a life-threatening disorder characterized by acute onset of progressive cutaneous hemorrhage, necrosis, and disseminated intravascular coagulation. Acute infectious PF occurs most commonly in the setting of meningococcal sepsis. When PF occurs in the setting of systemic lupus erythematosus (SLE), the catastrophic antiphospholipid antibody syndrome (CAPS) must be ruled out because urgent therapy is required. Plasmapheresis is effective in both cases, but immunosuppression (high-dose corticosteroids plus cyclophosphamide), although beneficial in patients with CAPS, could be harmful in patients with meningococcal PF. The authors report here a patient with SLE who presented to the intensive care unit with meningococcal PF, acute renal failure, and acute respiratory distress syndrome and discuss clinical similarities and laboratory differences from CAPS.
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PMID:Meningococcal purpura fulminans in a patient with systemic lupus erythematosus: a mimic for catastrophic antiphospholipid antibody syndrome? 1520 56

Endogenous generation of nitric oxide (NO) plays an important role in the regulation of cardiovascular and inflammatory responses. This mediator is synthesized by a family of enzymes collectively known as NO synthase. Several isoforms of this enzyme have been identified and can be grouped as constitutive or inducible. Increased production of NO is reported in several inflammatory disorders, such as sepsis, arthritis, thrombotic thrombocytopenic purpura (TTP), and antiphospholipid syndrome. In addition, NO upregulates cyclo-oxygenase-2 and synthesis of several other inflammatory cytokines. Inflammation and thrombotic complications are usually associated with malignancy. Earlier reports indicate the upregulation of tumor necrosis factor-alpha (TNF-alpha), C-reactive protein (CRP), and tissue factor (TF) in patients with malignancy. To determine the relationship between inflammatory cytokines and NO in cancer patients with hypercoagulable states, baseline plasma samples from 160 patients with confirmed malignancy and hypercoagulable state were analyzed for NO levels. A chemical method based on a chemiluminescent reaction between NO and ozone using a highly sensitive gas phase NO analyzer was used. CRP, TF, and TNF-alpha were measured using enzyme-linked immunosorbent assay methods. Of the 160 patients who were plasma tested, the baseline NO levels ranged from 13.7 to 98.6 microM (63.1+/-15.9 microM, mean+/-SD) in contrast to age-matched control, which ranged from 9.1 to 34.6 microM (19.8+/-6.2 microM, mean+/-SD, n=138). Cancer patients also showed marked variations in the NO levels. Eighteen of 60 cancer patients exhibited greater than 60 microM NO levels. The CRP, TNF-alpha and TF were also significantly elevated. A correlation between CRP (r(2)=0.73) and NO levels was noted in cancer patients with hypercoagulable state. These data suggest that the pathogenesis associated with malignancy/hypercoagulable state is associated with an inflammatory component. In addition, the observed hemodynamic changes in some of the cancer patients may be due to increased NO production.
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PMID:Blood levels of nitric oxide, C-reactive protein, and tumor necrosis factor-alpha are upregulated in patients with malignancy-associated hypercoagulable state: pathophysiologic implications. 1549 22

The case of a man with diagnosis of Kikuchi-Fujimoto disease (KFD) and catastrophic antiphospholipid syndrome (CAPS) is reported. He presented prolonged fever, lymphadenopathies, arthralgia, weight loss, hepatosplenomegaly and positive IgM for cytomegalovirus. While he was empirically treated with tuberculostatic drugs, he suddenly developed systemic inflammatory response syndrome, multiple organ failure and distal necrosis. On suspicion of severe sepsis, antibiotics, corticoids and recombinant human activated protein C (XIGRIS) were administrated. Exhaustive laboratory searching was negative. Histopathologic examinations of lymph node first disclosed malignant lymphoma but later KFD was confirmed. One month later, laboratory tests showed the presence of antiphospholipid antibodies (aPL). The patient was discharged after two months of hospitalization. This case exhibits a KFD complicated by definite CAPS. Cytomegalovirus could be involved in the development of both CAPS and KFD. Because of the severity of the case, we believe that XIGRIS noticeable improved the altered coagulation profile associated with CAPS.
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PMID:Catastrophic antiphospholipid syndrome and Kikuchi-Fujimoto disease: the first case reported. 1642 78

It is generally accepted that antiphospholipid syndrome remains a major medical problem characterised by hypercoagulability, arterial and venous thrombosis and thrombocytopenia. It is unclear how best to treat these patients should they require emergency surgery. If a lupus anticoagulant is present, hypercoagulability may occur de novo but surgical interventions along with sepsis are two important predisposing factors. We describe three patients with primary antiphospholipid syndrome and discuss the implications for surgery.
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PMID:Antiphospholipid syndrome: a series of surgical emergencies and the current evidence for its management. 1683 58

Emergency plasma exchange therapy is life saving in many cases. Therefore, clinicians must be aware of the indications at which any delay in initiating therapy may prove to be fatal. Different hematological (Moschkowitz-, hyperviscosity- and catastrophic antiphospholipid syndrome; massive haemolysis [e.g Wilson's disease]), neurological (myasthenic), endocrine (thyrotoxicosis) and nephrological (rapidly progressive glomerulonephritis) crisis situations and for prevention of them; certain poisonings, fulminant liver failure, severe pancreatitis due to chylomicronaemia, meningococcus sepsis and iatrogenic or suicidal drug-overdose. In this latter, it is of fundamental importance that the protein binding of the drug should be high (>80%), whereas the volume of its distribution should be relatively low (<0,2 l/kg body weight) and the endogenous clearance of it should be less, than 500 ml/min. Urgent leukocytapheresis should be performed above 50.000 blasts/microl, in acute or chronic myeloid leukemia if symptoms of leukostasis are present (if blasts are above 100.000/microl, cytoreduction is mandatory even without symptoms). Similarly, urgent thrombocytapheresis should be administered above platelet numbers 1000 G/l, when there is concomitant thrombophilia or clinical symptoms of thrombostasis are present.
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PMID:[Indications of urgent plasma exchange and cytapheresis therapies--a review based on literature data and personal experience]. 1706 1

The 'catastrophic' variant of the antiphospholipid syndrome (APS) is characterized by a diffuse thrombotic microvasculopathy. In contrast to the classical APS, single venous or arterial medium-to-large blood vessel occlusions are uncommon. The mechanisms of catastrophic APS are not clearly understood. In addition, there are no studies on pathophysiologic mechanisms of catastrophic APS. The clinical manifestations of catastrophic APS probably depend on (a) the organs affected by the thrombotic events and extent of the thrombosis and (b) manifestations of the systemic inflammatory response syndrome which are presumed to be due to excessive cytokine release from affected and necrotic tissues. The evident relationship between APS and infection may enable us to explain the development of catastrophic APS using the sepsis model. This is because catastrophic APS is characterized by multiple microvascular thrombotic events, of rapid onset, and causing multiorgan failure, a picture suggestive of septic shock, in which, there is a massive, acute inflammatory response.
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PMID:Laboratory studies on pathophysiology of the catastrophic antiphospholipid syndrome. 1713 45

Intestinal ischemia in antiphospholipid antibody syndrome (PAPS) could be due to arterial thrombosis from hypercoagulability. A male patient, 45 years old, was admitted to the hospital with symptoms of acute abdomen and after laparotomy he developed sepsis, right kidney infarction, jejunal ischemia, aortic thrombosis, wide necrosis of both gluteus muscles, left subclavian vein thrombosis. Our therapeutic and diagnostic strategy was delineated after demonstration of antiphospholipid antibodies. The patient was treated with total parenteral nutrition in the presence of 5 enteric fistulas with very high outflow, arterial stent insertion and daily changes of medicated dressings. Outcome was excellent with small residual deficit in walking. Continuous nutritional status monitoring and very high nitrogen supply allowed excellent healing of huge wounds and closure of enteral fistulas.
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PMID:[Acute abdomen in antiphospholipid antibodies syndrome (PAPS)]. 1736 35

Osteomyelites, bone infections of a hematogenous origin, are rare in the pelvis (2.3%) and are extremely rare in the ischium. Ischiatic osteomyelitis is usually found in children and adolescents, but has rarely been described in adults. The clinical presentation varies and the diagnosis is based on magnetic resonance imaging (MRI). The most frequently isolated germ is the staphylococcus, while Escherichia coli has been found in a few cases. We report a case of osteomyelitis from E. coli in a 46-year-old woman revealed by persistent fever. The point of entry was a septicemia from gastrointestinal origin, related to colon polyps. The clinical picture was also complicated by an antiphospholipid antibody syndrome (superior mesenteric vein and splenomesenteric branch thrombosis). The course was favorable thanks to appropriate antibiotic treatment and surgical debridment of the infection.
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PMID:Escherichia coli osteomyelitis of the ischium in an adult. 1994 63


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