Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012739 (disseminated intravascular coagulation)
 8,673 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hemostatic system is a dynamic evolving process that is age-dependent. Components of the hemostatic system are synthesized in early fetal life and do not cross the placenta from mother to fetus. However, plasma concentrations of proteins involved in hemostasis significantly differ from adults. Physiological reference ranges are available for premature infants, full-term infants and children from ages 1 to 16 years. In the coagulation system, plasma concentrations of the vitamin K-dependent and contact factors are decreased at birth, whereas other factors such as fibrinogen, FV, FVIII, and FXIII are similar or increased compared with adults at birth. In the fibrinolytic system, plasma concentrations of plasminogen are decreased at birth, whereas tissue plasminogen activator and plasminogen activator inhibitor are increased. Clinically, the hemostatic system of the young is effective and healthy infants do not suffer from spontaneous hemorrhagic complications. However, infants are more vulnerable, compared with older patients, for bleeding in the presence of either congenital or acquired haemostatic defects. Severe congenital bleeding disorders, although rare, frequently present in the newborn period. The most common acquired causes of bleeding newborns include disseminated intravascular coagulation, vitamin K deficiency, and liver disease. A description of these disorders and treatment guidelines are provided.
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PMID:The relevance of developmental hemostasis to hemorrhagic disorders of newborns. 919 36

Solvent/detergent virus-inactivated plasma (VIP) contains markedly reduced protein S (PS) and alpha 2-antiplasmin (APL) beside other slightly decreased inhibitors. This could possibly be critical for the balance of hemostasis in diseases in which plasma inhibitors are reduced. A heterogeneous group of 14 patients with 18 plasma transfusions (12 FFP/24 VIP, 2 units per transfusion) was investigated. The patients suffered from dilution coagulopathy, liver disease, disseminated intravascular coagulation (DIC), hyperfibrinolysis, or received massive transfusions. Prothrombin fragment 1 + 2, fibrin monomers, D-Dimers, thrombin-AT III complexes, antiplasmin-plasmin complexes and fibrinogen degradation products as markers of activated coagulation (MAC) were measured. Blood samples were taken before and after plasma replacement. Significant differences between VIP and FFP should be recognized by comparing the ratio of MAC after/MAC before plasma transfusion. Patients showed an average inhibitor plasma level of AT III 51%, protein C 44%, PS 63%, and APL 52%. Only the F 1 + 2 ratio was obviously higher in the VIP group but not significantly. So the remaining MAC ratios did not show any significant difference. Our preliminary data showed no indication for a higher state of activation of coagulation in patients receiving VIP in comparison with those receiving FFP, if the VIP had the quality required. Solvent/detergent (SD) inactivation of transfusion-relevant viruses in plasma was successfully performed by Horowitz et al. [1]. The procedure leads to a partial reduction of the activity of clotting factors [2]. PS and APL are more severely affected. Therefore, treatment with VIP might activate or at least increase the activation of coagulation, especially in patients with reduced plasma inhibitors. To clarify this problem, the following disorders with the indication for plasma replacement were included in a prospective randomized study of FFP vs. VIP: massive transfusion; dilution coagulopathy; disturbance in liver synthesis; disseminated intravascular coagulation (DIC); primary hyperfibrinolysis. Low PS levels could induce hypercoagulability by reduced F VIII and FV inhibition, and low APL could induce hyperfibrinolysis by reduced plasmin inhibition.
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PMID:Protocol and preliminary results of a clinical study for comparison of solvent/detergent-inactivated plasma VIP versus FFP with special consideration of the balance of hemostasis. 942 23

Twenty-two cats with liver disease were evaluated for coagulation abnormalities including alterations in prothrombin time, activated partial thromboplastin time, thrombin time, factor VII activity, and platelet count. The purpose of the study was to determine the prevalence of coagulation abnormalities in this population of cats, classify abnormalities according to underlying pathogenesis, and determine if serum biochemical parameters typically used as indicators of liver disease showed any correlation with the coagulation abnormalities present. Study results indicated that at least 1 coagulation abnormality was present in 82% of the cats. Prolongation of prothrombin time was most common (16/22 cats) and factor VII activity was below reference range (< 60%) in 15 cats. When classified according to underlying pathogenesis, vitamin K deficiency was the most common abnormality found (11/22). Other abnormalities were less common and included hepatic synthetic failure (3/22), indeterminate (3/22), and disseminated intravascular coagulation (1/22). Increase in alkaline phosphatase (ALP) activity was the only biochemical abnormality that showed statistically significant correlation with coagulation abnormalities (P = .023). Cats with marked increases in ALP activity were more likely to have coagulation abnormalities than those with only mild increases in ALP activity.
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PMID:Coagulation abnormalities in 22 cats with naturally occurring liver disease. 956 Jul 61

Four-factor PCCs are most frequently used for replacement of vitamin K-dependent clotting factors and inhibitors proteins C and S in patients bleeding after phenprocoumon or warfarin overdose, in vitamin K-deficient patients presenting life-threatening bleeding, and liver disease. Since many of these patients are prone to thromboembolic complications including DIC, all conceivable measures should be taken against the thrombogenic potential of PCC preparations. This thrombogenic potential of PCCs is obviously dependent on several factors including activated clotting factors, lack of inhibitors of blood coagulation, and coagulation factor overload, as well as predisposing factors referred to recipients and drug interactions. The composition of PCC should meet the following criteria: Antithrombin in addition to heparin for the neutralization of FIXa and FXa should be present in the preparations; no overloading with FII and FX; substantially lower FVII than FIX potencies in order to minimize contamination with or generation of FVIIa; and substantial protein C as well as protein S activities. Quality control should include determinations as recommended by the European Pharmacopoeia. Specific assays for quantification of FIXa and FXa are urgently required, and validity of these assays must be proven in surveys. All lots should also be tested for their FVIIa content. Furthermore, the safety of PCCs must be proven by suitable animal models. Whenever possible, patients receiving PCCs should be under low-dose heparin prophylaxis; simultaneous administration of heparin-neutralizing drugs or antifibrinolytic agents must be avoided.
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PMID:Production and composition of prothrombin complex concentrates: correlation between composition and therapeutic efficiency. 1049 3

Thrombogenicity of factor IX complex or prothrombin complex concentrates (PCC) is a well-acknowledged problem. The exact incidence is unknown but has decreased with the improvement of the quality of coagulation factor concentrates and a more judicious use of these products. The clinical spectrum of thrombogenicity ranges from superficial thrombophlebitis, deep-vein thrombosis and pulmonary embolism, and arterial thrombosis to disseminated intravascular coagulation. Several risk factors have been identified: (a) predisposing clinical factors (underlying disease and clinical condition), (b) therapy factors (dosing, concomitant therapy and drug interactions), and (c) quality of the PCC used. It is generally assumed that the risk of thromboembolic adverse effects is greater in patients with acquired disorders of hemostasis than in patients with inherited coagulation factor deficiencies. In hemophilia B, clinical conditions with an increased risk include large muscle hematomas, immobilization, surgery (especially orthopedic surgery), and liver disease. In acquired disorders of hemostasis, a prethrombotic state can be assumed in all patients where an indication for PCC concentrates is considered. Liver disease and/ or antithrombin deficiency are considered as major risk factors. Therapy factors with an increased risk include large, repetitive doses of PCC. It is assumed that heparin and, in the case of antithrombin deficiency, antithrombin substitution decrease the incidence of thromboembolic adverse effects. Heparin neutralisation with protamine and aprotinin therapy may be additional risk factors. The declining incidence and the recent cluster of fatal thromboembolic adverse events in Germany with one brand of PCC is strong evidence for the crucial role of the quality of PCC in the occurrence of thromboembolic adverse effects.
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PMID:Thrombogenicity of prothrombin complex concentrates. 1049 4

Background: Reduced levels of protein S (PS) and alpha(2)-antiplasmin alpha(2)-AP) in solvent/detergent virus-inactivated plasma (S/D-VIP) might induce an imbalance of plasma coagulation factors and inhibitors in patients transfused. We investigated 40 patients (23 fresh frozen plasma (FFP), 17 S/D-VIP, random distribution by a list calculated by statisticians) who suffered from dilution coagulopathy, liver disease, disseminated intravascular coagulation (DIC), polytrauma or were connected to extracorporeal circulation. Study Design and Methods: The following markers of activated coagulation (MAC) were measured: Prothrombin fragment F1+2 (F1+2), fibrin monomers (FM), D-dimers (DD), thrombin-antithrombin (TAT) and plasmin-antiplasmin (PAP) complexes as well as fibrinogen degradation products (FgDP), and additionally antithrombin III (antithrombin), protein C (PC), PS and alpha(2)-AP. Blood was taken only just before and 1 h after the first plasma replacement (2 units). No additional blood products were transfused before the second blood withdrawal. Pre- and posttransfusion (pre/post) values of all parameters measured were compared within the same group and between both groups. Statistical evaluation of the data was done by Wilcoxon's paired test for data in the same plasma group and by the test of Mann and Whitney for data comparison between both plasma groups. Results: Average pretransfusion values of all inhibitors for both plasma groups were in the same range and increased after transfusion, except for PS in both groups. Whereas the pre/post values did not differ significantly in the FFP group, antithrombin (p = 0.02), PC (p = 0.0005), and alpha(2)-AP (p = 0.02) showed a significantly higher increase in the S/D-VIP group. Considering the pre/post differences between both plasma groups, there were no significant differences. The same was true for MAC measured pre- and posttransfusion. Conclusion: Data showed no significant difference between both plasma groups, indicating that S/D-VIP plasma behaves as FFP under the study conditions employed. Copyright 2000 S. Karger GmbH, Freiburg
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PMID:Comparison of Solvent/Detergent-Inactivated Plasma and Fresh Frozen Plasma under Routine Clinical Conditions. 1087 83

The incidence and clinical manifestations of disseminated intravascular coagulation (DIC) were examined in patients with a range of underlying disorders. Out of 1,882 patients suspected as having DIC, 204 cases were diagnosed as suffering from DIC and included in this study. The underlying disorders experienced by the patients were solid tumors (33.8%), hematologic malignancies (12.7%), aortic aneurysm (10.8%), infections (6.4%), post-operative complications (4.4%), liver disease (2.9%), obstetric disorders (2.5%), and miscellaneous diseases (26.5%). The incidence of DIC was 10.8% out of all patients suspected of having DIC, and the etiologies were 10.9% in solid tumors, 10.1% in hematological malignancies, 20.4% in aortic aneurysm, 12.7% in infections, 15.5% in post-operative complications, 15.8% in liver disease, 3.7% in obstetric disorders, and 9.8% in miscellaneous diseases. The clinical manifestations of DIC patients were varying dependent on their etiologies. Most DIC patients with aortic aneurysm (95.5%) and post-operative complications (88.9%) did not reveal any clinical manifestations. Although all of the patients with obstetric disorders had bleeding, only 20.0% of the patients had organ failure. In contrast, although only 15.4% of the patients with infections had bleeding, 76.9% of these patients had organ failure. Bleeding was observed in 31.9-50.0% of DIC patients with liver disease, hematologic malignancies, and solid tumors. Organ failure was observed in 21.7-33.3% of DIC patients with liver disease, hematological malignancies, and solid tumors. Analysis by measurement of plasma levels of antiplasmin and plasmin-antiplasmin complex suggested that excessive fibrinolysis might contribute to the development of bleeding in these DIC patients. Differences in plasma levels of thrombin-antithrombin complex and cross-linked fibrin degradation products could not account for the differences in the incidence of organ failure in the patients. These findings suggest that the clinical manifestation of DIC varies and might not only be a reflection of microthrombus formation but also a reflection of the other underlying pathomechanisms.
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PMID:Heterogeneity in the incidence and clinical manifestations of disseminated intravascular coagulation: a study of 204 cases. 1107 38

The management of unexpected bleeding must be directed at the specific abnormality identified, as there is no universally effective and safe procoagulant product. Where practical, a purely pharmaceutical approach obviates the residual risks of exposure to plasma-derived products. Desmopressin is often effective in bleeding due to mild haemophilia A, Type I von Willebrand's disease and some platelet function disorders. Where replacement therapy is necessary, it should be as specific as possible, preferably using purified components singly or in combination. Recombinant proteins provide the greatest margin of safety, but it must be borne in mind that these are biologicals, and that they may contain human and animal plasma-derived proteins. Where specific replacement is unavailable or impractical, plasma or crudely fractionated plasma derivatives may be used. In the case of inhibitor antibodies to factor VIII, high dose human factor VIII or porcine factor VIII may be used. Where replacement therapy is impossible due to a high inhibitory titre, it may be necessary to bypass the specific haemostatic defect using activated prothrombin complex concentrates or recombinant activated factor VIIa. The latter product is being studied in patients with various disorders of platelet function, and in the more global haemostatic failure that accompanies end-stage liver disease. Ancillary methods are often of great value in securing haemostasis. These may be derived from pharmacological or biological sources, and their sites of action may be systemic or topical. Examples include antifibrinolytic lysine analogues, corticosteroids where inflammation accompanies bleeding, and the topical application of fibrin sealants or thrombin. Simple physical measures such as pressure, ice, or splinting are also valuable adjunctive measures. Finally, it must be emphasized that the ultimate control of bleeding often depends upon effective management of the inciting cause, such as eliminating the trigger for DIC, or suppressing the causative antibody of ITP. These principles will be presented using a practical algorithmic approach. The initial question when considering treatment should be whether or not the patient is acutely unstable. Instability may be due to one of two causes: the volume of blood loss leading to a compromised cardio-vascular status, or the site of the bleed. The relevance of the site of the bleed is independent of the volume of blood loss, so for example, a closed bleed into CNS will cause critical functional compromise even though the volume of bleeding may be minimal. Similarly bleeding into a compartment, such as into a forearm or a calf will cause critical functional compromise irrespective of the volume of bleeding.
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PMID:Unexpected bleeding disorders: Algorithm for approach to therapy. 1125 56

Increased sensitivity to warfarin anticoagulation is usually attributed to liver disease, vitamin K deficiency, or drug interactions. We describe a patient with unexplained sensitivity to warfarin and mildly elevated prostate-specific antigen levels in whom subsequent developments indicated that warfarin sensitivity was the first manifestation of occult prostatic cancer. A review of all published cases of coagulopathy associated with cancer of the prostate shows that, unlike other solid tumors with secondary disseminated intravascular coagulation (DIC), in prostate cancer increased bleeding is more common than thrombotic phenomena. Chronic DIC due to occult prostate cancer should be included in the differential diagnosis of excessive prothrombin time prolongation in patients receiving anticoagulants.
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PMID:Increased warfarin sensitivity as an early manifestation of occult prostate cancer with chronic disseminated intravascular coagulation. 1140 12

Beriplex, a prothrombin complex concentrate (PCC), was administered to 42 patients requiring immediate reversal of their oral anticoagulant therapy. The dose administered was determined using the pretreatment International Normalized Ratio (INR). Blood samples were obtained before treatment and at 20, 60 and 120 min after treatment. The following investigations were performed on all samples - INR, clotting factors II, VII, IX and X, coagulation inhibitors protein C (PC) and antithrombin (AT), and other markers of disseminated intravascular coagulation, plasma fibrinogen, D-dimer and platelet count. Immediate reversal of the INR, the vitamin K-dependent clotting factors and PC was achieved in virtually all patients. Reduced AT levels were present in 18 patients before treatment. Further slight AT reductions occurred in four patients, but other associated abnormalities of haemostasis were observed in only one of the four patients. One patient with severe peripheral vascular disease, sepsis and renal and cardiac failure died of a thrombotic stroke following leg amputation, 48 h after receiving Beriplex. No other arterial and no venous thromboembolic events occurred within 7 d of treatment. Beriplex is effective in rapidly reversing the anticoagulant effects of warfarin, including PC deficiency, without inducing coagulation activation. Caution should continue to be exercised in the use of these products in patients with disseminated intravascular coagulation, sepsis or liver disease.
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PMID:Rapid reversal of oral anticoagulation with warfarin by a prothrombin complex concentrate (Beriplex): efficacy and safety in 42 patients. 1184 21


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