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Use of factor-VII-rich prothrombin complex concentrate in liver disease.

A prothrombin complex concentrate rich in factor VII has been used in the management of the clotting defect in thirteen patients with liver disease. Adequate correction of coagulation was achieved immediately after infusion in all cases. Within 4 hours there was some deterioration and by 24 hours the results approximated to pre-fusion values. Liver biopsies were performed without haemorrhagic complication in the immediate post-infusion period. There was no evidence of induced intravascular coagulation. Since other prothrombin complex concentrates have proved disappointing, both in their failure to correct the clotting defect and in their production of disseminated intravascular coagulation, this factor-VII-rich concentrate may be the treatment of choice in patients with liver disease who require temporary correction of their coagulation defect.

Blood Coagulation Disorders

Correction of abnormal coagulation in chronic liver disease by combined use of fresh-frozen plasma and prothrombin complex concentrates.

The effect on abnormal coagulation tests of infusions of fresh-frozen plasma (F.F.P), prothrombin complex concentrates, and a combination of these treatments was compared in 30 patients with chronic liver disease undergoing needle biopsy. A single dose of F.F.P. (12 ml/kg body-weight) was found to be the least effective therapeutic regimen. The concentrate containing factors II, IX, and X was also not adequate, but the additional administration of factor-VII concentrate corrected the prothrombin-time (P.T.) and "Normotest" (N.T.) in most patients. However, this regimen did not correct the prolonged kaolin activated partial thromboplastin-time (K.P.T.T.). The results of tests for exploring both the extrinsic (P.T. and N.T.) and intrinsic (K.P.T.T.) coagulation systems only became normal after the combined administration of a lower dose of F.F.P. (8 ml/kg body-weight) and of both concentrates (12 units/ml). There was no clinical or laboratory evidence of thrombotic complications. No patient developed acute hepatitis or hepatitis-B surface antigen in the twelve months after biopsy. These results indicate that prothrombin-complex concentrates in combination with F.F.P. may therefore be used to allow liver biopsy to be performed safely in patients presenting with severe coagulation defects.

Biopsy

Prothrombin complex concentrates: potentially thrombogenic materials and clues to the mechanism of thrombosis in vivo.

Factors affecting the coagulant activity of two different prothrombin complex concentrates have been investigated using a sensitive in vitro assay developed in this laboratory. One concentrate contained substantial amounts of potentially thrombogenic material, while the other, which was deliberately fortified with antithrombin III and heparin during production, was judged to be relatively nonthrombogenic. The coagulant activity of the thrombogenic concentrate has been partially identified and was due largely to the presence of coagulation factos IXa and Xa. Neither concentrate contained detectable thrombin. However, after incubation with calcium or various polyamines, large amounts of additional coagulant material, including thrombin, appeared. Heparin and antithrombin III not only neutralized the thrombogenic materials present in the thrombogenic concentrate, but also inhibited the de novo generation of coagulant enzymes during incubation with calcium. The implication of these studies on the preparation of prothrombin complex concentrates and on host susceptibility to thrombosis during the clinical use of these concentrates is discussed.

Antithrombins

[Emergency treatment of haemophilia A with factor VIII inhibitors using activated prothrombin complex concentrates (author's transl)].

Severe rectal bleeding in a 6-year-old boy with haemophilia A and factor VIII inhibitors could not be stopped with factor VIII concentrates. But a good effect was achieved with activated prothrombin complex concentrates (fraction FEIBA), given over eight days. Amaurosis occurred as a complication after injection of the first dose, but disappeared completely within several minutes. Tests revealed accelerated intravascular coagulation with increased fibrin monomers and fibrin/fibrinogen degradation products.

Blindness

A randomized study of factor VIII or prothrombin complex concentrate infusions in children with haemophilia and antibodies to factor VIII.

In four children with haemophilia A and antibodies to factor VIII, 18 bleeding episodes were randomized for treatment with factor VIII concentrate (30 units/kg) and 18 for treatment with a prothrombin-complex concentrate (prothrombinex) given in a dose of 30 units of factor IX/kg. Treatment with prothrombinex was associated with a better clinical response, a significantly greater shortening of the kaolin partial thromboplastin time and significantly lower incidence of post-infusion increase of levels of factor VIII antibodies. Although treatment with factor VIII concentrate was clinically successful in 15 episodes, treatment failures occurred in three instances leading to parental request for withdrawal from study in two families.

Antibodies

Prothrombin complex concentrate (PCC) vs. non-PCC strategies for warfarin reversal in left ventricular assist device recipients: A systematic review and meta-analysis.

BACKGROUND: Left ventricular assist devices (LVADs) prolong survival in end-stage heart failure, and warfarin thromboprophylaxis is recommended to prevent device thrombosis and thromboembolic complications. When bleeding occurs or emergency surgery is required, rapid anticoagulation reversal is critical. Prothrombin complex concentrate (PCC) provides rapid reversal; however, its risk-benefit profile in LVAD recipients remains unclear. We conducted a systematic review and meta-analysis comparing PCC with non-PCC strategies for warfarin reversal in LVAD recipients. METHODS: MEDLINE, Embase, and Scopus were searched through June 2025 for studies of PCC versus non-PCC strategies for warfarin reversal in LVAD recipients. Two reviewers independently extracted data. Random-effects models were used to pool arm-level estimates and to pool head-to-head comparisons using mean differences or risk ratios (RRs). RESULTS: Eighteen studies involving 779 patients were included. Arm-level pooled estimates for PCC versus non-PCC comparators were 24.0% versus 15.8% for mortality, 16.5% versus 12.1% for thrombotic events, and 3.1 versus 5.7 for FFP units. Arm-level time to INR correction was longer with PCC overall (16.5 versus 13.6 h), driven by one elective cohort, but faster within the ICH subgroup (6.0 versus 13.7 h). In head-to-head comparisons, PCC achieved faster INR correction than non-PCC comparators (mean difference - 7.6 h; p = 0.001) and required fewer FFP units (-2.6 units; p = 0.019), with no significant difference in all-cause mortality (RR 1.14; p = 0.490) or thrombotic events (RR 1.43; p = 0.176). CONCLUSIONS: In head-to-head studies, PCC was associated with faster INR correction and lower FFP requirements than non-PCC strategies, whereas mortality and thrombotic events did not differ significantly. Given the observational evidence, wide confidence intervals, and heterogeneity, equivalent safety cannot be established, and prospective studies are needed to define the relative safety and effectiveness of the two approaches. IMPLICATIONS FOR CLINICAL PRACTICE: PCC-based strategies may be considered for urgent warfarin reversal in LVAD recipients, particularly when rapid INR reduction or avoidance of large-volume plasma transfusion is clinically important. Treatment decisions should account for the indication, bleeding severity, and underlying thrombotic risk. TRIAL REGISTRATION: CRD42024573925.

Humans

Effect of treatment with activated prothrombin complex concentrate (FEIBA) on factor VIII-antibody level.

The influence of treatment with an activated prothrombin complex preparation (FEIBA) on the antibody level was studied in 10 haemophiliacs with an antibody to factor VIII. The antibody level was observed to rise at least once in five patients, while in the remaining five patients no rise occurred. In all, 6 out of 31 treatments were followed by an anamnestic rise of the antibody level, corresponding to 19.4%. A rise of the inhibitor level following FEIBA treatment is likely to occur in patients who show a marked antibody rise after factor VIII treatment (good responders), but have a low antibody level at the time of treatment. High doses of FEIBA and simultaneous of red cells may also enhance the likelihood of an anamnestic response. Stimulation of antibody production is probably due to the presence of small amounts of factor VIII in this preparation.

Antibodies

[Pharmacokinetic aspects of overdosage and intoxication with oral anticoagulant drugs (author's transl)].

Three aspects of treatment with oral anticoagulant drugs are discussed: 1. Drug interactions which can lead to changes in the elimination or distribution of oral anticoagulant drugs with special emphasis on the time course of the augmentation of the anticoagulant effect. 2. Pharmacokinetic factors responsible for inter- and intrasubject differences in the response to oral anticoagulant drugs. 3. Treatment of overdosage and intoxication with oral anticoagulant drugs. Besides symptomatic treatment with vitamin K and prothrombin complex concentrate the interruption of the enterohepatic recycling by cholestyramine is demonstrated as a useful method for enhancing the elimination of phenprocoumon and warfarin from the body.

Administration, Oral

The use of pluronic polyols in the precipitation of plasma proteins and its application in the preparation of plasma derivatives.

Pluronic F-38 was used a precipitant of plasma proteins under varying conditions of pH and polymer concentration. Results indicated that marked differences in the solubility of the plasma proteins in F-38 solutions can be appled to the separation of plasma components. The feasibility of the industrial application of this fractionation method was tested in several experiments. Conditions were established for the preparation of albumin, human plasma protein fraction (HPPF), and immune serum globulin (ISG) with similar yield and purity as those prepared by the Cohn methods. Current procedures for the preparation of antihemophilic A (Facor VIII) concentrate and prothrombin complex (Factors II, VII, IX, and X) were adapted to the F-38 process by removal of the clotting factors from the starting plasma prior to polymer precipitation. In addition, a plasma protein solution free of lipoproteins, isoagglutinins, and clotting factors was developed which has proven useful as a perfusion medium in organ preservation.

Blood Preservation

[Effect of surface roughness of polymers on thrombus formation].

Thromboresistant properties of fluoroplast-4, lavsan, polymethylmetacrylate, carbon glass, employed in various devices contacting the blood and presenting different degrees of the surface roughness, were studied. The thromboresistant properties of polymers were judged on the ground of modified methods for determining the blood coagulating time, thromboelastograms, with reference to the prothrombin complex factors concentration, the amount of fibrinogen, heparin blood tolerance, the thrombocytes adhesion index, their splitting and flattening. A higher class of the polymer surface roughness was found to raise the thromboresistant properties of the surface. In case of polymers with high mechanical and strength properties the surface roughness is of greater importance in the genesis of thrombosis than in polymers possessing elastic properties.

Biocompatible Materials

Coagulative and fibrinolytic studies on postmenopausal women treated with a new non-steroidal oestrogen.

Treatment of postmenopausal women with a non-steroid oestrogen (P1496) in a dose of 50 mg a day for 2 ,days before operation for prolapse did not suppress the histochemically determined fibrinolytic activator content of the vessel wall. Neither was any change found in the concentration of P&P-complex (prothrombin, factor VII, factor X), factor VIII, antithrombin III, alpha1-antitrypsin, alpha2-macroglobulin or the inhibitors of urokinase induced plasminogen activation. Nothing suggested a thrombogenic effect of this non-steroidal oestrogenic compound.

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