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Results for “Prothrombin complex concentrate”

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PubMed1997

[Acquired haemophilia A].

A 74-year-old man developed a severe bleeding disorder on the basis of acquired Factor VIII (F VIII) inhibitor. Coagulation assays showed a prolonged activated partial thromboplastin time (APTT) with a normal prothrombin time (PT);F VIII level was 0.07 IU and F VIII inhibitor level 8.8 Bethesda units (BU). At least half the cases of acquired haemophilia A are associated with pregnancy, the postpartum period or an underlying malignancy or autoimmune disease. Haemorrhagic diathesis can be severe and life-threatening. Treatment of acute haemorrhages consists of human or porcine factor VIII concentrate, activated prothrombin complex concentrate (FEIBA) or recombinant factor VIIa, depending on the antibody titre. Immunosuppressive therapy is successful in at least 60% of the patients in making the inhibitor disappear. In patients with a spontaneous haemorrhagic diathesis, a thorough medical history should be taken, coagulation assays should be performed and a specialist should be consulted.

Aged↗

PubMed1999

Recombinant factor VIIa does not induce hypercoagulability in vitro.

Recombinant factor VIIa (rVIIa) has been reported to be clinically effective and safe in haemophilic patients with inhibitor antibodies. Compared to activated prothrombin complex concentrates the risk of thrombotic complications seems to be very low after rVIIa administration. Determination of free thrombin generation has been shown to identify hypercoagulability. Therefore, free thrombin and prothrombinase activity (Xa generation) were assessed after extrinsic activation of rVIIa supplemented factor VIII and factor IX deficient plasma. Free thrombin generation was also determined after supplementation of (activated) prothrombin complex concentrates. Addition of 150 U rVIIa/ml shortened the clotting times markedly in control, factor VIII, and factor IX deficient plasma. In contrast, free thrombin and Xa generation were not different in the absence or presence of 150 U rVIIa/ml. Addition of (activated) prothrombin complex concentrates resulted in a marked increase of free thrombin generation in all investigated plasmas. Although in vitro studies cannot reflect specific clinical circumstances our results support the notion that rVIIa does not induce a hypercoagulable state as sporadically observed after administration of (activated) prothrombin complex concentrates.

Blood Coagulation↗

PubMed1985

Multiple extractions in a patient with factor VII deficiency.

Multiple extractions were carried out in a patient with factor VII deficiency treated with prothrombin complex concentrate. Hemostasis and healing were completely satisfactory. The side effects of prothrombin complex concentrate are discussed.

Blood Coagulation Factors↗

PubMed1998

The effect of recombinant factor VIIa (NovoSeven) in healthy volunteers receiving acenocoumarol to an International Normalized Ratio above 2.0.

Vitamin K antagonists are most commonly used in long-term thrombosis prophylaxis and the use in patients with cardiovascular disease seems to be increasing. By interfering with the normal hemostatic mechanism, an increased risk of bleeding will arise and administration of human plasma or prothrombin complex concentrates may be necessary. It can be difficult to normalize hemostasis using plasma and prothrombin complex concentrates, because these may be associated with thromboembolic side-effects. The level of factor VII, one of the vitamin-K-dependent coagulation factors, decreases during oral anticoagulant therapy and the administration of recombinant factor VIIa normalizes the prolonged prothrombin time in warfarin-treated rats. After administration of acenocoumarol (International Normalized Ratio > 2), decreased levels of factor X and factor IX (19-46%), protein C (2-20%) and factor VII (4-17%) were found in 28 healthy volunteers. After one dose of recombinant factor VIIa (5, 10, 20, 40, 80, 120, 160, 240, or 320 microg/kg) the International Normalized Ratio and prothrombin time normalized, which may imply an effect on bleeding in individuals receiving oral anticoagulant therapy. The lowest dose (5 microg/kg) normalized the International Normalized Ratio for 12 h and doses > 120 microg/kg normalized it for 24 h. Fragment 1+2 stayed within its normal range in all dose groups, indicating that no systemic coagulation occurred.

Acenocoumarol↗

PubMed1994

[Outcome of hemorrhage treatment in children with hemophilia A related to factor VIII inhibitor].

The results of bleedings treatment in 11 children with haemophilia A and factor VIII (f. VIII) inhibitor was presented. Concentrates of human and porcine f. VIII and activated prothrombin complex concentrate were used in the treatment. The method of treatment depended on the level of human and porcine f. VIII inhibitors. In patients with level of human f. VIII inhibitor lower than 10 jB/ml the concentrates of human f. VIII in doses 2-3 times higher than usually used in haemophiliacs without inhibitor were successful. When inhibitor level was higher than 10 jB/ml, but low cross-reactivity of porcine f. VIII was stated, concentrates of porcine f. VIII were used with good result. In children with high level of antibody against human and porcine f. VIII, the best results were achieved using activated prothrombin complex concentrates.

Adolescent↗

PubMed1994

Markers of hypercoagulability in patients with hemophilia B given repeated, large doses of factor IX concentrates during and after surgery.

Purer factor IX (FIX) concentrates have been produced for the treatment of hemophilia B in the attempt to reduce the risk of thrombotic complications associated with the use of prothrombin complex concentrates. To evaluate ex vivo whether or not FIX concentrates activate the coagulation system in conditions associated with a high risk for thrombosis, we measured markers of hypercoagulability in 10 patients with hemophilia B who underwent surgery, mainly orthopedic procedures, covered by multiple concentrate infusions (40-80 U/kg/day). Postinfusion plasma levels of prothrombin fragment 1 + 2 and factor X activation peptide did not differ significantly from the presurgical levels, neither before nor after each concentrate dose. Therefore, it appears that prolonged treatment of patients with hemophilia B undergoing high risk surgical procedures with high doses of FIX concentrate does not cause systemic activation of coagulation. This suggests that purified FIX concentrates are preferable to prothrombin complex concentrates for conditions associated with an increased risk of thrombosis.

Adolescent↗

PubMed2005

Intracerebral hemorrhage associated with oral anticoagulant therapy: current practices and unresolved questions.

BACKGROUND AND PURPOSE: Life-threatening intracranial hemorrhage, predominantly intracerebral hemorrhage (ICH), is the most serious complication of oral anticoagulant therapy (OAT), with mortality in excess of 50%. Early intervention focuses on rapid correction of coagulopathy in order to prevent continued bleeding. SUMMARY OF REVIEW: This article reviews the epidemiology of OAT-associated ICH (OAT-ICH), and current treatment options, with the aim of providing a framework for future studies of unresolved questions. A number of acute treatments are available, but all have a significant risk of inducing thrombosis and other side effects, and vary in their rapidity of effect: vitamin K (very slow response time), fresh frozen plasma (slow response time, large volume of fluid required, transfusion-related acute lung injury), prothrombin complex concentrates, and recombinant activated factor VII. Current practice is to administer a combination of vitamin K and either fresh frozen plasma or prothrombin complex concentrates; the occasional use of recombinant activated factor VII has been reported. No prospective study has addressed the efficacy of, or outcomes from, the use of these practices. CONCLUSIONS: Current management of OAT-ICH is varied and not based on evidence from randomized controlled trials. Well-designed clinical trials are essential if we are to identify the effective acute treatments for OAT-ICH that are urgently needed.

Administration, Oral↗

PubMed2007

Anticoagulants and their reversal.

In an exciting era with many alternatives to the old anticoagulants heparin and warfarin emerging on the scene, awareness of the possibility to reverse their effect is mandatory. In this review, the traditional antidotes for warfarin (vitamin K, plasma, and prothrombin complex concentrate) and for heparin (protamine) are described together with the newer alternatives (recombinant activated factor VII, concatameric peptides, and recombinant platelet factor 4). For some of the newer anticoagulants, possible antidotes have been identified, whereas other alternatives have been discarded. There is a very limited experience of deamino-d-arginine vasopressin or a von Willebrand factor VIII concentrate to counteract hirudin. The small direct thrombin inhibitors may be reversed with activated prothrombin complex concentrate but not with recombinant activated factor VII, whereas the latter agent appears to be effective against the pentasaccharides and the recombinant nematode anticoagulant protein C2. Additional options that may become available in the future are also discussed briefly.

Anticoagulants↗

PubMed1995

Measurement of activated factor IX in factor IX concentrates: correlation with in vivo thrombogenicity.

Current in vitro tests for thrombogenicity of FIX concentrates used for prothrombin complex concentrates (PCCs), are of little value when applied to high purity FIX (HP FIXs). In the present study, we have developed a chromogenic assay for activated FIX (FIXa) and evaluated its ability to predict in vivo thrombogenic potential of HP FIXs in a modified Wessler stasis model. Among the HP FIXs, only 1 out of 7 products had no detectable FIXa; this product also showed no in vivo thrombogenicity. In the other 6 products, FIXa content ranged from 0.15-1.2 U/1000 in FIX, and all showed some evidence of in vivo thrombogenicity, with mean thrombus scores ranging from 0.25-4. There was a significant positive correlation (r = 0.55, p < 0.02) between FIXa levels and in vivo thrombogenicity of HP FIXs. NAPTT data were not significantly correlated with the in vivo results and the TFCT also showed no direct correlation with the mean thrombus score. These results indicate that HP FIXs may still carry a small residual thrombotic risk and measurement of FIXa content of these products may be a better predictor of thrombogenicity than the current in vitro tests.

Animals↗

PubMed1992

[Hemophiliacs with inhibitor. Experience at the Center of Medical Action for Hemophilia of the S. José Hospital].

Factor VIII inhibitors arise in 5% to 15% of patients with hemophilia A in response to infusion to factor VIII concentrates and make the treatment of bleeding episodes extremely difficult. Various therapeutic approaches have been tried the decision depending on the type of haemorrhage, the antibody's titre and whether the patient has a low or high response. We report the clinical experience in 13 hemophiliacs with inhibitors to factor VIII. Prothrombin complex concentrates were administered with favorable effects in the most common haemorrhagic episodes, in the majority of patients. In two patients activated prothrombin complex concentrates were administered and in one case plasma exchange was made before high doses of factor VIII. These therapeutic approaches proved to be very effective in the control of hemostasis.

Adolescent↗

PubMed1990

Acute myocardial infarction, non-bacterial thrombotic endocarditis, and disseminated intravascular coagulation in a severe hemophiliac.

Thrombosis in hemophilia is very rare and is usually associated with the administration of prothrombin complex concentrates. We describe a severe hemophiliac with P. carinii pneumonia who had clinical and laboratory evidence of acute myocardial infarction and disseminated intravascular coagulation, and at autopsy, nonbacterial thrombotic endocarditis as well. We suggest that prothrombin complex concentrates should be used cautiously in the setting of acute infection, and perhaps be given with appropriate doses of anticoagulants such as heparin.

Adult↗

PubMed1984

Elective cardiac operation in a patient with severe hemophilia and acquired factor VIII antibodies.

This paper describes a successful cardiac operation in a young boy with hemophilia, congenital heart disease, severe factor VIII deficiency, and an acquired high titer antibody to factor VIII. To our knowledge, there have been no published cases of elective cardiac operations in a person with severe hemophilia and an accompanying complex problem. Utilizing the team approach, we administered a megadose bolus of factor VIII concentrate preoperatively (eight times the calculated dose), followed by a continuous intravenous infusion at 500 units/hr throughout the procedure and at a reduced dose for the first 5 postoperative days. With the anamnestic rise in factor VIII antibody on day 5, activated prothrombin complex concentrates were substituted for factor VIII and provided continued adequate hemostasis during the remaining 9 postoperative days. The rapid infusion of large quantities of factor VIII was effective in neutralizing the low titer inhibitor and providing normal hemostasis during the procedure. In addition, activated prothrombin complex concentrates were substituted for factor VIII coagulant without recurrent bleeding or thromboembolic phenomena.

Antibodies↗

PubMed2005

Impact of introducing guidelines on anticoagulant reversal.

The production of clinical guidelines has become an accepted and lauded part of modern medicine. It is also widely perceived that these guidelines provide some sort of panacea for the problems that medicine faces. Our experience suggests otherwise. Triggered by on going anecdotal evidence of poor practice, we reviewed the effect on practice of a recently introduced local guideline on the management of major bleeding in patients on warfarin. Comparing 34 patients treated before and 48 patients after the introduction of the guideline, we found no significant improvement in prothrombin complex concentrate dosing or administration of vitamin K. The only improvement witnessed was in early assessment of the effect of the intervention on coagulation which improved from 10 to 35% of cases. Of major concern, in 10% of cases, there was no documentation to confirm or refute that prothrombin complex concentrate (PCC), which had been issued, had actually been administered to the patient. The production and widespread dissemination of this local guideline did not achieve significant improvement in clinical practice. Possible reasons for failure to adhere to the guideline are discussed.

Anticoagulants↗

PubMed2002

[Factor X deficiency and pregnancy].

Factor X deficiency is one of the rarest inherited coagulation disorders. It is an autosomal recessive inherited disease. In its homozygous form factor X deficiency has an estimated prevalence of 1: 500,000. However in its heterozygous form it has an estimated frequency of 1: 500 to 1: 2000. Pregnancy in women with congenital factor X deficiency has been associated with adverse foetal outcomes. We report a case of pregnancy in a woman with factor X deficiency. She was treated early during labour with prophylactic replacement of prothrombin complex concentrates (Kaskadil). An initial infusion of 40 UI.kg-1 of factor X was followed by 20 UI.kg-1 every 24 hours during three days. During labour and peripartum maternal coagulation was screened. She delivered a healthy baby at 33 weeks of gestation. No episode of abnormal bleeding was observed. Therefore in this case, prophylactic therapy using prothrombin complex concentrates during labour and delivery did prevent severe haemorrhages.

Adult↗

PubMed1993

Human coagulation factor IX: assessment of thrombogenicity in animal models and viral safety.

Thromboembolic complications associated with prothrombin complex concentrate treatment may be related to the high levels of factors II and X in these products. We report here results from preclinical safety studies with a human coagulation factor IX product (AlphaNine; Alpha Therapeutic Corp., Los Angeles, Calif.) that contains no detectable factor II or VII and less than 10 units of factor X/100 units of factor IX. This product was manufactured from virally inactivated factor IX complex with a barium citrate adsorption step followed by affinity chromatography yielding factor IX concentrate with a specific activity of about 86 factor IX units/mg protein. Electrophoresis and immunoblot analysis indicated that the factor IX represents about 65% of the protein in this product. The virus inactivation step incorporated into the manufacturing process (incubation with n-heptane at 60 degrees C for 20 hours) was shown to inactivate at least 8.6 logs of type 1 human immunodeficiency virus. The barium citrate adsorption and affinity chromatography steps were found to remove 2.0 logs of the marker virus, vaccinia, and the DEAE ion-exchange chromatography used to produce factor IX complex was found to remove 1.4 logs of the marker virus, Sindbis. Analysis of three separate manufacturing lots with the polymerase chain reaction revealed no evidence of hepatitis C virus. The purified factor IX was nonthrombogenic when tested at doses of 450 units/kilogram in a rabbit stasis (Wessler) model, whereas the prothrombin complex concentrates were found to be thrombogenic at doses of less than 50 units/kg. There was no evidence of DIC in a porcine model after infusion of 200 units/kg of coagulation factor IX, as manifested by negative fibrin monomer tests, the absence of fibrin in blood vessels at autopsy, little or no change in prothrombin times and partial thromboplastin times, and only moderate decreases in platelet levels after infusion.

Animals↗

PubMed1983

Anti-inhibitor coagulant complex (Autoplex) in hemophilia inhibitor patients undergoing synovectomy.

Surgical synovectomy employed in the management of hemophilic arthropathy has been contraindicated in patients with inhibitors because of potential difficulties in achieving hemostasis. However, the development of activated prothrombin-complex concentrates has improved the management of hemophiliacs with inhibitors, particularly those with high levels of inhibitor for whom other treatment modalities are of minimal benefit. With the use of one of these activated products, Autoplex, surgical procedures have been successfully accomplished in hemophiliacs with inhibitors. Two inhibitor patients who each had severe arthropathy of one knee underwent elective surgical synovectomy while being treated with Autoplex. Hemostasis was achieved during the perioperative period in both patients. Neither patient exhibited clinical signs of suggestive of consumptive coagulopathy or thrombosis, side effects potentially associated with the use of activated prothrombin-complex concentrates.

Adolescent↗

PubMed2001

Heart transplant in a factor VIII-deficient patient with a high-titre inhibitor: perioperative management using high-dose continuous infusion factor VIII and recombinant factor VIIa.

Four years prior to transplantation, a 14-year-old boy with severe haemophilia A and a high-responding factor VIII (FVIII) inhibitor developed an anteroseptal myocardial infarct while receiving high doses of an activated prothrombin complex concentrate (PCC). Cardiac transplantation was required for survival because of the ensuing cardiomyopathy. At surgery, the patient's inhibitor titre was 1.8 Bethesda units (BU). High-dose bolus therapy, followed by a continuous infusion of FVIII provided excellent operative and initial postoperative haemostasis without additional blood-product support. Once anamnaesis developed on day 6 postoperatively, recombinant factor VIIa (rFVIIa) therapy was initiated. Haemostasis remained excellent, except for the transient increase in chest-tube bleeding that was noted on day 7. epsilon-Aminocaproic acid was added and haemostasis was re-established. On day 15, rFVIIa was replaced with alternate day infusions of prothrombin complex concentrates (PCCs). On day 21 following the transplant, the patient was discharged, remaining on daily FVIII immune tolerance and thrice-weekly PCC prophylaxis. He remains well 24 months after transplant with an inhibitor titre of 39 BU. This paper describes the second case of cardiac transplantation complicated by haemophilia and an inhibitor, and discusses preoperative planning and operative and postsurgical haemostasis management.

Adolescent↗

PubMed1984

Coagulation proteins showing abnormal electrophoretic mobility in commercial concentrates of factor VIII and prothrombin complex.

Five commercial factor VIII (FVIII) concentrates and three prothrombin complex concentrates (PCC) were studied with reference to the qualitative evaluation of factors II, IX, fibronectin, alpha 2-antiplasmin (alpha 2-AP), antithrombin III (AT-III) and subunits A and S of FXIII by crossed-immunoelectrophoresis (CIE) and von Willebrand factor antigen (vWF:Ag) by radio-CIE. This latter protein had a different pattern with the absence or a decrease of larger forms and the presence of a fast-moving precipitating peak, suggesting degradation of the vWF:Ag in FVIII concentrates. In contrast, the electrophoretic mobility of fibronectin, alpha 2-AP and AT-III was normal. All PCC showed a more anodic mobility of factor IX. alpha 2-AP also exhibited a different electrophoretic pattern to that of normal plasma. Abnormality of AT-III was also found in heparin-binding studies. The techniques used in the purification procedures are probably the mechanism responsible for the partial denaturing of these proteins.

Antithrombin III↗