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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Canine cyclic hematopoiesis (CH) is an autosomal recessive disease of gray collie dogs that is characterized by 14-day cycles of neutropenia, monocytosis, thrombocytosis, and reticulocytosis. Platelets from CH dogs have decreased dense-granule serotonin pools and decreased aggregation responses to collagen, platelet-activating factor (PAF), and thrombin. Recombinant granulocyte colony-stimulating factor (rG-CSF) was administered (5 micrograms/kg, b.i.d.) to four CH and six normal dogs to determine if G-CSF therapy corrected qualitative platelet defects in CH dogs. Neutrophil counts increase to greater than 25,000 cells/microliters within 24 h after starting treatment in all dogs. Treatment with G-CSF blocked neutropenic episodes in the CH dogs. Platelet aggregation, and serotonin content and secretion were significantly (p less than 0.05) decreased in the CH dogs both before and during recombinant human (rh) G-CSF treatment compared to normal dogs. Neutrophil myeloperoxidase, a primary granule enzyme, was significantly (p less than 0.05) decreased in CH dogs and was not corrected by rhG-CSF treatment. Administration of rG-CSF to CH dogs eliminated cell cycles but apparently did not correct cellular defects in CH dogs. Identification of primary biochemical defects in cells from CH dogs may be crucial to investigating the biochemical basis for cyclic hematopoiesis.
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PMID:Effects of recombinant granulocyte colony-stimulating factor treatment on hematopoietic cycles and cellular defects associated with canine cyclic hematopoiesis. 169 76

We examined the role of leukocytes in the pathogenesis of lung vascular injury induced by thrombin in awake sheep prepared with the lung lymph fistulas. Thrombin (80 U/kg) infusion in control sheep (n = 6) increased pulmonary arterial pressure (Ppa) twofold and pulmonary vascular resistance (PVR) three-fold for the 5-h experimental period. Thrombin also increased pulmonary vascular permeability to protein as assessed by decrease in the reflection coefficient (sigma) from 0.70 +/- 0.03 to 0.61 +/- 0.01. Thrombin caused similar initial pulmonary hemodynamic changes in sheep rendered neutropenic (n = 7; 2% neutrophil count of controls) by treatment with hydroxyurea; however, both Ppa and PVR returned toward base-line values within 120 min postthrombin challenge. The increases in pulmonary lymph flow and transvascular protein clearance also recovered rapidly beginning at 60 min after challenge with thrombin in neutropenic sheep. Neutropenia prevented the increase in lung vascular permeability as the sigma value of 0.71 +/- 0.02 was similar to the control value. Leukocytes isolated from control donor sheep were infused intra-arterially into recipient neutropenic sheep (n = 4) to assess the effects of neutrophil repletion on the pulmonary vascular responses. Thrombin (80 U/kg) challenge infused at 1-3 h after infusion of leukocytes increased lung lymph flow twofold and transvascular protein clearance fourfold and produced increases in Ppa and PVR comparable with the control group. The increases in these parameters were sustained for the 5-h experiment duration. The data indicate the essential pathogenetic role of neutrophils in mediating the thrombin-induced increase in lung vascular permeability.
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PMID:Leukocyte repletion reverses protective effect of neutropenia in thrombin-induced increase in lung vascular permeability. 237 1

Platelet activating factor (PAF) has many proinflammatory properties. It is a polymorphonuclear leukocyte chemotactic factor, it aggregates platelets, increases vascular permeability, and is generated by inflammatory cells. To determine the possible in vivo role of PAF in inflammation, we examined the effects of the PAF antagonist and structural analogue, CV3988 on acute inflammatory responses in the skin of rabbits. Initial experiments indicated that CV3988 (10 mg/kg) was a specific inhibitor of PAF responses in vivo since it abolished neutropenia and thrombocytopenia induced by intravenous (iv) PAF infusion without effecting the response to f-met-leu-phe. In dermal inflammation, 125I-albumin, 111In-labeled platelets, 51Cr-labeled leukocytes, and 86RbCl were used to simultaneously quantitate protein exudation, platelet deposition, leukocyte accumulation, and blood flow in the lesions. CV3988 inhibited inflammatory responses to intradermal injection of PAF by 65 to 85% but it did not inhibit thrombin-induced platelet deposition or bradykinin and histamine-induced protein exudation. CV3988 treatment inhibited by 60 to 80% (p less than 0.01) the platelet deposition occurring at the peak of the reaction (1 1/2 hours) induced by the intradermal injection of zymosan, zymosan activated plasma, endotoxin, and the reversed passive Arthus reaction. Protein exudation was inhibited by 67 to 85% (p less than 0.1) and leukocyte accumulation was inhibited by 24 to 35% (p less than 0.05), but only in the zymosan and reversed passive Arthus reactions, respectively. Inflammatory hyperemia (increases blood flow) was not affected by CV3988 treatment. We conclude that in certain inflammatory reactions, PAF may mediate platelet deposition and protein exudation. The marginal effect of CV3988 on leukocyte accumulation suggests that the leukotactic activity of PAF is relatively less important in vivo.
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PMID:Evidence that platelet activating factor may mediate some acute inflammatory responses. Studies with the platelet-activating factor antagonist, CV3988. 395 Nov 99

Platelets can release a variety of inflammatory mediators. These formed elements have been shown to accumulate early in acute inflammation, often prior to fibrin and thrombus formation. Polymorphonuclear leukocyte (PMNL) infiltration is also an early event and is linked to protein exudation and hyperemia. The relationship between PMNL and platelet accumulation was studied. Inflammation was induced in rabbits by intradermal injection of stimuli, and 51Cr-labeled leukocytes and 111In-labeled platelets were used to quantitate the rates of leukocyte and platelet accumulation in the dermal reactions. A temporal association between the rates of leukocyte infiltration (greater than 95% PMNL) and of platelet deposition at skin sites was observed when killed Escherichia coli, E. coli-derived chemotactic factors, zymosan-activated plasma, f-met-leu-phe, or endotoxin were injected intradermally. A linear correlation (r = 0.96; p less than 0.001) between these parameters was observed. 59Fe-labeled red cells did not accumulate in these lesions. Platelet deposition in response to inflammatory stimuli did not occur in PMNL-depleted (nitrogen mustard treatment) but platelet-sufficient rabbits, in spite of normal platelet deposition in thrombin-injected sites. Platelet responses to inflammatory stimuli were normal when neutropenia, after nitrogen mustard treatment, was prevented. In contrast, in situ PMNL reconstitution of the skin sites in neutropenic rabbits did not cause local platelet accumulation. Intravenous infusion of the synthetic chemotactic factor, f-met-leu-phe, induced transient neutropenia and thrombocytopenia (30% of control) with platelet sequestration primarily in the lung. This is also the known site of PMNL sequestration during f-met-leu-phe infusion. It is concluded that platelets selectively deposit in acutely inflamed tissues primarily during PMNL margination in, and emigration across, the microvasculature. Platelets and PMNLs likely coassociate on the vessel wall, and this interaction may influence the course of inflammation.
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PMID:Role of neutrophils in the deposition of platelets during acute inflammation. 636 76

Hematologic abnormalities were studied prospectively in 38 patients with brucellosis. Anemia was found in 74% of patients, leukopenia in 45%, neutropenia in 21%, lymphopenia in 63%, and thrombocytopenia in 39.5%. Eight patients (21%) were pancytopenic; seven of these individuals also had splenomegaly. Bone marrow hypoplasia was not found. Bleeding complications developed in 26% of patients and were significantly associated with clotting abnormalities (low platelet count, low fibrinogen level, and/or prolongation of thrombin clotting time); i.e., bleeding occurred in approximately 50% of patients with marked clotting abnormalities but in no patients with normal clotting. Determination of fibrinogen levels at different stages of brucellosis led to a redefinition of the normal level for patients with this infection. Patients without clotting abnormalities had fibrinogen levels of 233-711 mg/100 ml (mean, 384 mg/100 ml), whereas patients with thrombocytopenia and prolonged thrombin clotting time had levels of 122-360 mg/100 ml (mean, 216 mg/100 ml; P less than .001) that increased to 233-519 mg/100 (mean, 360 mg/100 ml) when clotting values returned to normal. Lymphopenia was significantly correlated with the severity of clinical manifestations (bleeding and hepatic involvement).
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PMID:Hematologic changes in brucellosis. 648 Nov 87

Detailed coagulation studies were done prospectively on 43 patients with biliary atresia who had undergone Kasai operation (hepatic portoenterostomy). Patients were divided into three groups based on levels of factor V, factor II, and Echis II and/or response to vitamin K: no coagulopathy (46.5% of patients); coagulopathy of liver disease (30.2% of patients); and coagulopathy of vitamin K deficiency (23.3% of patients). Patients with the coagulopathy of liver disease had significantly lower levels of factors XII, V, and antithrombin III as well as longer thrombin times than patients with no coagulopathy or vitamin K deficiency. Factor V levels were decreased only in patients with more advanced liver disease; normal levels of factor V were not usually helpful in differentiating liver disease and vitamin K deficiency. The prothrombin time, factor VII-X levels, and factor II levels were significantly different for all three groups; the most abnormal values occurred in the vitamin K-deficient group. Comparison of the Echis II level to factor II coagulant activity was helpful in deciding whether a coagulopathy was due to liver disease, vitamin K deficiency, or both. Factor VIII levels were elevated in all groups. Factor VIII coagulant activity was significantly higher by the two-stage (TGT) method than by the one-stage (PTT) method. Hypersplenism causing neutropenia and thrombocytopenia was commonly seen after the age of 5 years. Vitamin E deficiency was more common than vitamin K deficiency; however, all vitamin K-deficient patients were vitamin E deficient. Coagulation status correlated well with hepatobiliary scan data, but not serum bilirubin levels. Recommendations for treatment of patients with vitamin K deficiency and/or liver disease are discussed.
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PMID:The multiple coagulopathies of biliary atresia. 669 16

Exposure of human blood polymorphonuclear leukocytes (PMN) to purified active plasma kallikrein resulted in PMN aggregation when kallikrein was present at concentrations ranging from 0.4 to 0.6 U/ml (0.18-0.27 microM). Kallikrein-induced PMN aggregation was not mediated through C5-derived peptides, because identical responses were observed whether or not kallikrein had been preincubated with an antibody to C5. Moreover, kallikrein was specific for aggregating PMN, because no aggregation was observed with Factor XII active fragments (23 nM), Factor XIa (0.6 U/ml or 15nM), thrombin (1.6 microM), plasmin (2 microM), porcine pancreatic elastase (2 microM), bovine pancreatic chymotrypsin (2 microM), or bradykinin (1 microM). Bovine pancreatic trypsin (2 microM) aggregated PMN, but to a lesser extent than kallikrein (0.18 microM). Kallikrein was a potent aggregant agent for PMN because similar responses were observed with kallikrein (0.5 U/ml or 0.23 microM) and an optimal dose (0.2 microM) of N-formyl-methionyl-leucyl-phenylalanine. In addition, PMN incubation with kallikrein resulted in stimulation of their oxidative metabolism as assessed by an increased oxygen uptake. Neutropenia and leukostasis observed in diseases associated with activation of the contact phase system may be the result of PMN aggregation by plasma kallikrein.
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PMID:Purified human plasma kallikrein aggregates human blood neutrophils. 691 55

Infection of naive North American horses with 10(4) cell culture infectious doses (CCID50) of virulence variants of African horsesickness virus (AHSV), designated AHSV/4SP, AHSV/9PI, and AHSV/4PI, reproduced three classical forms of African horsesickness: acute (pulmonary), subacute (cardiac), and febrile, respectively. Distinct clinicopathologic and hemostatic abnormalities were associated with each form of disease. Hemostatic abnormalities included increased concentration of fibrin degradation products and prolongation of prothrombin, activated partial thromboplastin, and thrombin clotting times. Hemostatic findings indicated activation of the coagulation and fibrinolytic systems with clotting factor consumption in acute and subacute cases of African horsesickness. Hematologic abnormalities in acute and subacute cases of African horsesickness included leukopenia, decreased platelet counts, elevated hematocrit, and increased erythrocyte counts and hemoglobin concentration. Leukopenia was characterized by lymphopenia, neutropenia, and a left shift. Increased levels of serum creatine kinase, lactate dehydrogenase, aspartate aminotransferase, and alkaline phosphatase, hypocalcemia, hypoalbuminemia, hypoproteinemia, and elevated creatinine, phosphorus, and total bilirubin levels were present in some but not all horses. Metabolic acidosis, indicated by decreased total bicarbonate and increased lactate and anion gap, was present in horses with the acute form of disease. Mild thrombocytopenia and leukopenia were occasionally associated with the febrile form of disease. These results suggest a role for intravascular coagulation in the pathogenesis of African horsesickness.
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PMID:Clinical pathology and hemostatic abnormalities in experimental African horsesickness. 777 Oct 50

Solute transport and alterations in complement and clotting induced by a new high-flux cellulose acetate membrane (CA-HF800-E, Diaphan) were compared with those for cellulose triacetate (CTA) and polysulphone in a cross-over clinical study. The membranes are similar in their small-molecule removal. Serum beta 2-microglobulin decreased with all membranes but the decrease was independent of membrane type. Associated with beta 2-microglobulin removal was a protein loss which averaged 2636 mg for Diaphan, 4937 mg for CTA, and 2500 mg for polysulphone. Albumin presence in the dialysate was less than the limit of detection (5 mg/l) but for each of the membranes, occasional readings above the limit of detection were noted. C3a generation for Diaphan is comparable with that for CTA and polysulphone, but differed for C5a and neutropenia. A highly significant correlation of the area under the concentration time curve of the two complement components was noted for the cellulose based membranes (r = 0.875, P = 0.0002 for Diaphan, r = 0.823, P = 0.006 for CTA) this relationship was less marked for polysulphone (r = 0.396, P = 0.29). Induction of clotting characterized by the thrombin-antithrombin III (TAT) complex were similar for the three membranes, as were changes in platelet counts. Our findings indicate that while it is possible to modify cellulose to produce a membrane whose solute transport and biocompatibility is similar to synthetic membranes such as polysulphone, the structural modifications induce considerable differences in the amount of protein lost.
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PMID:Clinical comparison of high-flux cellulose acetate and synthetic membranes. 817 78

Septic shock and multiple organ failure may be associated with coagulation activation, disseminated fibrin formation, and consumption of coagulation inhibitors such as antithrombin III. We have evaluated prospectively coagulation measurements in patients with severe chemotherapy-induced neutropenia. This group of patients was chosen because of their high risk of developing severe septic complications, thus allowing serial prospective coagulation testing before and during evolving sepsis or septic shock. Sixty-two patients with febrile infectious events were accrued to the study. Of these, 13 patients progressed to severe sepsis and 13 additional patients to septic shock as defined according to standard diagnostic criteria. At the onset of fever, factor (F) VIIa activity, FVII antigen and antithrombin III (AT III) activity decreased from normal baseline levels and were significantly lower in the group of patients who progressed to septic shock compared with those that developed severe sepsis (medians: 0.3 v 1.4 ng/mL, 21 v 86 U/dL and 45% v 95%; P < .001). The decrease of these measurements in septic shock was accompanied by an increase in prothrombin fragment 1+2 (median: 3.6 v 1.4 nmol/L; P = .05), a marker of thrombin generation. These differences were sustained throughout the septic episode (P < .0001). FVIIa and AT III levels of < 0.8 ng/mL and < 70%, respectively, at onset of fever predicted a lethal outcome with a sensitivity of 100% and 85%, and a specificity of 75% and 85%, respectively. In contrast, FXIIa-alpha antigen levels were not different between groups at onset of fever but increased modestly during the course of septic shock (P = .001). Thus, septic shock in neutropenic patients is associated with increased thrombin generation. Furthermore, both FVIIa and AT III measurements are sensitive markers of an unfavorable prognosis.
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PMID:Factor VIIa and antithrombin III activity during severe sepsis and septic shock in neutropenic patients. 916 Jul 2


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