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 kinetics of thrombin generation in various prothrombin-complex-preparations (PCC) were investigated using a chromogenic substrate assay. The rate of thrombin formation and the total activity of thrombin generated varied considerably among different preparations. The thrombin generation velocity influenced the rate of fibrinogen to fibrin conversion, measured as plasma viscosity alteration per unit of time. It also influenced thrombin induced platelet aggregation with regard to maximum aggregation and aggregation velocity. The kinetic parameters measured photometrically and coagulometrically showed reduced generation velocities and less thrombin effects with thrombin formed in PCCs than with thrombin generated in plasma. The quantitative differences between thrombin effects in various PCCs on platelet aggregation did not correlate with the data of the amidolytic and fibrinogenolytic measurements. The significance of the results is discussed with regard to the question of whether, or to what extent, PCCs could cause or accelerate a disseminated intravascular coagulation.
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PMID:Thrombin generation in prothrombin-complex-preparations; its effect on a chromogenic substrate, fibrinogen and platelets. 223 26

To test the value of diagnostic and therapeutic data in obstetric DIC, 14 women were selected who presented a severe clotless haemorrhage with fibrin degradation products and/or soluble complexes, decreased fibrinogen (0.87 +/- 0.47 g X 1(-1)), platelet count (75.7 +/- 41 X 10(3) X ml-1) and prothrombin complex (33.7 +/- 12%). The hypovolaemia was treated at the same time as heparin was given in a bolus injection of 0.5 mg X kg-1 followed by a constant flow infusion of 1 mg X kg-1 X day-1 in all patients. Relevant obstetrical treatment was performed in 71.4% of patients. Fibrinogen, fresh frozen plasma, prothrombin complex concentrate and platelet concentrate were given if required. One patient, with severe toxaemia, died. Haemorrhage was stopped in 92.8% of patients after 4.5 +/- 0.8 h. Reversible visceral complications occurred in 28% of cases. The initial data used was easily obtained and seemed to give a reliable diagnosis in acute obstetrical DIC. Substitutive treatment was discussed in correlation with the evolution: PCC seemed pointless; the use of fibrinogen must become exceptional when fresh frozen plasma is available. Heparin remained necessary.
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PMID:[Disseminated intravascular coagulation. Retrospective study of 14 acute obstetrical cases]. 665 Sep 31

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

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