Biochemical comparison of seven commercially available prothrombin complex concentrates

Kalina, Uwe; Bickhard, Heike; Schulte, Stefan

doi:10.1111/j.1742-1241.2008.01859.x

Cited by 83 publications

(72 citation statements)

References 26 publications

(23 reference statements)

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“…With one exception - Uman Complex (Kedrion, Castelvecchio Pascoli, Italy), which contained negligible factor VII - coagulation factor levels were broadly similar in all seven products, and all tested negative for activated coagulation factors [9]. There were, however, some differences in coagulation inhibitor levels (Figure 2), resulting in different thrombin inhibitory capacities.…”

Section: Differences Between Today's Pccs and Older Productsmentioning

confidence: 99%

“…There were also considerable purity differences between the products. It is noteworthy that all of the PCCs contained considerable concentrations of prothrombin (factor II), and that S-TIM 4 or Prothromplex (Baxter, Vienna, Austria) had a higher factor II:factor IX ratio than the other products [9]. …”

Section: Differences Between Today's Pccs and Older Productsmentioning

confidence: 99%

“…Protein C, protein S and protein Z contents of different prothrombin complex concentrates (PCCs) [9]. …”

Section: Differences Between Today's Pccs and Older Productsmentioning

confidence: 99%

“…A recent study of PCC constituents found broad correlation with the products' labelled values [9]. In most currently available PCCs, the factors are found in the inactivated form.…”

Section: Introductionmentioning

confidence: 99%

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Clinical review: Prothrombin complex concentrates - evaluation of safety and thrombogenicity

et al. 2011

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Prothrombin complex concentrates (PCCs) are used mainly for emergency reversal of vitamin K antagonist therapy. Historically, the major drawback with PCCs has been the risk of thrombotic complications. The aims of the present review are to examine thrombotic complications reported with PCCs, and to compare the safety of PCCs with human fresh frozen plasma. The risk of thrombotic complications may be increased by underlying disease, high or frequent PCC dosing, and poorly balanced PCC constituents. The causes of PCC thrombogenicity remain uncertain but accumulating evidence indicates the importance of factor II (prothrombin). With the inclusion of coagulation inhibitors and other manufacturing improvements, today's PCCs may be considered safer than earlier products. PCCs may be considered preferable to fresh frozen plasma for emergency anticoagulant reversal, and this is reflected in the latest British and American guidelines. Care should be taken to avoid excessive substitution with prothrombin, however, and accurate monitoring of patients' coagulation status may allow thrombotic risk to be reduced. The risk of a thrombotic complication due to treatment with PCCs should be weighed against the need for rapid and effective correction of coagulopathy.

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Section: Differences Between Today's Pccs and Older Productsmentioning

confidence: 99%

Section: Differences Between Today's Pccs and Older Productsmentioning

confidence: 99%

“…Protein C, protein S and protein Z contents of different prothrombin complex concentrates (PCCs) [9]. …”

Section: Differences Between Today's Pccs and Older Productsmentioning

confidence: 99%

“…A recent study of PCC constituents found broad correlation with the products' labelled values [9]. In most currently available PCCs, the factors are found in the inactivated form.…”

Section: Introductionmentioning

confidence: 99%

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Clinical review: Prothrombin complex concentrates - evaluation of safety and thrombogenicity

et al. 2011

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“…Table I [4,5] displays the composition of currently available PCCs. PCCs typically contain 3 (Factors II, IX, and X) or 4 (Factors II, VII, IX, and X) clotting factors derived from human plasma that has undergone virus reduction [6,7].…”

Section: Prothrombin Complex Concentrates Compositionmentioning

confidence: 99%

Prothrombin complex concentrates in emergency bleeding disorders

Rodgers

2012

American J Hematol

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The use of prothrombin complex concentrates (PCCs), a heterogeneous combination of coagulation factors and counterbalancing inhibitor components, has broadened in recent years beyond single‐factor replacement in conditions such as hemophilia B, to encompass emergency reversal of anticoagulation secondary to oral vitamin K antagonists, ie, warfarin therapy. PCCs also have been studied in other bleeding disorders, such as surgery‐related and trauma‐related bleeding. This review provides an updated examination of the differences among PCC formulations, their potential role in the management of bleeding disorders, and the primary safety issues affecting their use. Am. J. Hematol. 2012. © 2012 Wiley Periodicals, Inc.

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Vitamin K Antagonist Reversal for Urgent Surgery Using 4-Factor Prothrombin Complex Concentrates

Sarode,

Goldstein,

Simonian

et al. 2024

JAMA Netw Open

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ImportanceMillions of people take vitamin K antagonists (VKAs). Some people who need urgent surgical procedures require rapid VKA reversal to prevent excessive intraoperative bleeding.ObjectiveTo evaluate the hemostatic noninferiority of an investigational 4-factor prothrombin complex concentrate (4F-PCC) to a control 4F-PCC for rapid VKA reversal before urgent surgery.Design, Setting, and ParticipantsThis phase 3, double-blind, noninferiority randomized clinical trial (LEX-209) was conducted in 24 hospitals in the US, Russia, Georgia, Belarus, Ukraine, and Romania from June 7, 2017, through November 8, 2021; the study was stopped in February 2022. Participants were adult patients taking VKA who had an international normalized ratio (INR) of 2 or higher and needed urgent surgery with a substantial bleeding risk (≥50 mL). Patients were randomized 1:1 to a single infusion of either the investigational 4F-PCC or the control 4F-PCC. Data analysis followed intention-to-treat and per-protocol approaches.InterventionsSingle intravenous infusion was dosed by body weight and baseline INR. A dose of 25, 35, or 50 IU/kg of investigational 4F-PCC or control 4F-PCC was administered for baseline INR of 2 to less than 4, 4 to 6, or over 6, respectively.Main Outcome and MeasureThe primary end point was hemostatic efficacy at surgery end. An independent adjudication board, blinded to the 4F-PCC treatment allocation, assessed hemostatic efficacy using an objective 4-point scale.ResultsA total of 208 patients (median [range] age, 67.5 [31-92] years; 118 males [56.7%]) received the investigational (n = 105) or the control (n = 103) 4F-PCC. The median (range) dose was 25 (16-50) IU/kg in the investigational group and 25 (15-50) IU/kg in the control group, with a median (range) infusion time of 12 (8-50) minutes and 13 (7-30) minutes and a median (range) time from infusion to surgery start of 1.42 (0.25-15.25) hours and 1.50 (0.42-18.50) hours, respectively. Baseline median (range) INR was 3.05 (1.97-21.10) in the investigational group and 3.00 (2.00-11.30) in the control group. In the intention-to-treat analysis, the investigational 4F-PCC was noninferior to the control 4F-PCC, resulting in effective hemostasis in 94.3% of patients vs 94.2% of patients (proportion difference, 0.001; 95% CI, −0.080 to 0.082; P &lt; .001), meeting the prespecified noninferiority margin of 0.15. An INR of 1.5 or lower at 30 minutes after infusion occurred in 78.1% of patients in the investigational group vs 71.8% of patients in the control group (proportion difference, 0.063; 95% CI, −0.056 to 0.181). Thrombotic events (2.9% vs 0%, respectively) and mortality (4.8% vs 1.0%, respectively) were no different than expected for 4F-PCC use. One patient in each treatment group discontinued due to adverse events (cardiac disorders unrelated to 4F-PCC).Conclusions and RelevanceThis randomized clinical trial found that the investigational 4F-PCC was hemostatically noninferior to the control 4F-PCC for rapid VKA reversal in patients needing urgent surgery with considerable bleeding risk; the safety profile of these two 4F-PCCs was similar. These results support the investigational 4F-PCC as a therapeutic option for surgical patients requiring rapid VKA reversal.Trial RegistrationClinicalTrials.gov Identifier: NCT02740335

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Biochemical comparison of seven commercially available prothrombin complex concentrates

Abstract: This in vitro study showed considerable differences between PCCs in terms of coagulation inhibitory capacity and purity.

Cited by 83 publications

References 26 publications

Clinical review: Prothrombin complex concentrates - evaluation of safety and thrombogenicity

Clinical review: Prothrombin complex concentrates - evaluation of safety and thrombogenicity

Prothrombin complex concentrates in emergency bleeding disorders

Vitamin K Antagonist Reversal for Urgent Surgery Using 4-Factor Prothrombin Complex Concentrates

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