This page shows what was measured, who it was measured in, and what that does not settle.
What Four-Factor Prothrombin Complex Concentrate does in the body
Putting back the clotting proteins that warfarin has switched off, in someone who is bleeding badly or needs surgery within hours
Warfarin works by stopping your liver from finishing four of the proteins that make blood clot. This product is those four proteins, purified from donated human plasma and freeze-dried into a small vial. Injected, it puts the finished proteins straight back into circulation, so clotting resumes within minutes rather than waiting for the liver to catch up. It also contains proteins C and S, the body’s own brakes, which are included precisely because a bolus of pure clotting factors would otherwise be dangerous.
What happened in people
No reduction in 24-hour blood product consumption in trauma (12 versus 11 units, p=0.72), with thromboembolic events at 35% against 24% (relative risk 1.48, 95% CI 1.04 to 2.10)
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The recorded finding that sits closest to something a person would notice. Written into the record, not signed off, and it carries no population or interval.
Goldstein JN, Refaai MA, Milling TJ Jr, et al. Four-factor prothrombin complex concentrate versus plasma for rapid vitamin K antagonist reversal in patients … · a recorded source, not a stored snapshot
That faster INR correction than plasma means fewer deaths — never compared, in thirteen years on the United States market
Where it acts
Blood plasma — the factors circulate and are consumed at the site of injury
Kind of result
A number that stands in for health
Supervision
RNAWiki has not recorded a supervision or regulatory status for this substance.
Where each sentence above came from
No recorded sentence describes the change this makes in a way that stands on its own. The page opens with what it is taken for instead, and the recorded explanation follows below.
Shown as the opening line on this page.
A limit recorded against this substance. Not signed off as a reviewed claim.
The four opening statements run to 140 words.
Words this page uses
Four words worth knowing first
Chosen from what this page shows, with each one explained before the word it depends on.
Comparator
A comparator is whatever the treatment was measured against.
A picture of it, and where the picture fails
It is like the other runner in a race.
Where that stops being true. A race has one winner. A study can show both arms improved.
What people get wrong. Results are read without asking what the other group got. Beating nothing is not beating a treatment.
The control condition against which the experimental intervention is assessed.
Randomisation
Randomisation means chance decides who gets which treatment.
A picture of it, and where the picture fails
It is like a coin toss deciding the groups.
Where that stops being true. A coin toss is fair once. Fairness here comes from doing it for everyone.
What people get wrong. It is thought to make groups identical. It makes them similar on average, including on things nobody measured.
Allocation of participants to arms by a chance process, so that unmeasured factors are balanced in expectation.
Absolute difference
An absolute difference is how many more people in a hundred were affected.
A picture of it, and where the picture fails
It is like counting heads in two rooms of a hundred.
Where that stops being true. Heads are easy to count. Study results carry a margin of error too.
What people get wrong. It is confused with a percentage change, which can look far larger.
The arithmetic difference in event rates between arms.
Confidence interval
A confidence interval is the range the true answer is likely to sit in.
A picture of it, and where the picture fails
It is like a weather forecast giving a range rather than one number.
Where that stops being true. A forecast range covers tomorrow. This one covers what the study could resolve.
What people get wrong. The middle number is read as the answer. A range crossing zero means no change is still possible.
An interval estimate that would contain the true parameter in a stated proportion of repeated studies.
What happened in people◇Read from sources, not yet reviewed
What happened in people
Each card is one study: the exact question it asked, who was in it, and whether it showed what it set out to show.
Co-primary: 24-hour haemostatic efficacy from start of infusion, and INR correction to 1.3 or below at 0.5 hours
✓ The study showed what it set out to show
Who was studied
NCT00708435 — four-factor prothrombin complex concentrate versus plasma in major bleeding on vitamin K antagonists
Effective haemostasis 72.4% versus 65.4% (difference 7.1%, 95% CI -5.8 to 19.9, non-inferior); rapid INR reduction 62.2% versus 9.6% (difference 52.6%, 95% CI 39.4 to 65.9, superior)
Repeated elsewhere
Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. Open-label design with an adjudicated haemostatic efficacy endpoint. Deaths and thromboembolic events were similar between arms at a sample size that could not have detected a difference in either.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Intravenous infusion of a reconstituted lyophilised concentrate, given once
Interval reported. 95% CI -5
Written into the record, not signed off as a reviewed claim.
Goldstein JN, Refaai MA, Milling TJ Jr, et al. Four-factor prothrombin complex concentrate versus plasma for rapid vitamin K antagonist reversal in patients … · a recorded source, not a stored snapshot
Co-primary: effective haemostasis, and rapid INR reduction to 1.3 or below at 0.5 hours after infusion end
✓ The study showed what it set out to show
Who was studied
NCT00803101 — four-factor prothrombin complex concentrate versus plasma before urgent surgery
How many people
181
Study design
Phase 3b multicentre open-label randomised non-inferiority then superiority trial
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Effective haemostasis 90% versus 75% (difference 14.3%, 95% CI 2.8 to 25.8, superior); rapid INR reduction 55% versus 10% (difference 45.3%, 95% CI 31.9 to 56.4, superior)
Repeated elsewhere
Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. Funded by the manufacturer and open-label. Thromboembolic adverse events 7% versus 8%; fluid overload or similar cardiac events 3% versus 13%, which is the advantage that comes from volume rather than from pharmacology.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Intravenous infusion of a reconstituted lyophilised concentrate, given once
Interval reported. 95% CI 2
Written into the record, not signed off as a reviewed claim.
Goldstein JN, Refaai MA, Milling TJ Jr, et al. Four-factor prothrombin complex concentrate versus plasma for rapid vitamin K antagonist reversal in patients … · a recorded source, not a stored snapshot
PROCOAG (NCT03218722) — 4F-PCC in trauma at risk of massive transfusion
How many people
324
Study design
Double-blind randomised placebo-controlled superiority trial, 12 level I trauma centres
Compared against
A dummy treatment
Kind of result
A number that stands in for health
What was found
Median 12 units versus 11 units, absolute difference 0.2 units (95% CI -2.99 to 3.33), p = 0.72
Repeated elsewhere
Unreplicated
What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.
The limits of this study, and where it came from
Main limit. At least one thromboembolic event in 35% versus 24%, relative risk 1.48 (95% CI 1.04 to 2.10), p = 0.03. The authors state the findings do not support systematic use in this population.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Intravenous infusion of a reconstituted lyophilised concentrate, given once
Interval reported. 95% CI -2
Written into the record, not signed off as a reviewed claim.
Goldstein JN, Refaai MA, Milling TJ Jr, et al. Four-factor prothrombin complex concentrate versus plasma for rapid vitamin K antagonist reversal in patients … · a recorded source, not a stored snapshot
Composite haemostatic efficacy at 12 hours, as the comparator against andexanet alfa
✗ The study did not show it
Who was studied
ANNEXA-I usual-care arm (NCT03661528) — the largest controlled dataset on this product for direct oral anticoagulant reversal
How many people
267
Study design
Randomised comparator arm within a phase 4 trial of andexanet alfa
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Haemostatic efficacy 53.1% on usual care against 67.0% on andexanet; thrombotic events 5.6% against 10.3%; no appreciable difference in modified Rankin scale or 30-day death
Repeated elsewhere
Unreplicated
What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.
The limits of this study, and where it came from
Main limit. This is not a trial of prothrombin complex concentrate; it is a trial in which the concentrate happened to be what 85.5% of the control arm received. There has never been a randomised trial of this product against placebo or against no reversal in direct oral anticoagulant bleeding.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Intravenous infusion of a reconstituted lyophilised concentrate, given once
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Goldstein JN, Refaai MA, Milling TJ Jr, et al. Four-factor prothrombin complex concentrate versus plasma for rapid vitamin K antagonist reversal in patients … · a recorded source, not a stored snapshot
RNAWiki holds 4 written-up human studies for this substance, each with the question it asked.
How we know it
Each card names the study, the number of people and what the study set out to measure.
What this does not prove
These summaries were written by a person and have not been signed off as reviewed claims.
Why it matters
A study that failed is as informative as one that worked, and both are here.
What we still do not know
No reviewed claim exists, so no exact population, effect size or interval is published yet.
What it changes in the body◇Read from sources, not yet reviewed
The path through the body
From what a person takes to what changes. A solid line is a step measured in people. A dashed line is a step nobody has measured that way.
Start
Four-Factor Prothrombin Complex Concentrate
What a person takes: Intravenous infusion of a reconstituted lyophilised concentrate, given once.
The measurement behind this step
Supplied as a freeze-dried powder with diluent, reconstituted at the bedside and infused over minutes. Vitamin K is given alongside it in every protocol, because the concentrate covers only the hours until the liver resumes making its own factors. There is no other route.
Getting in
A small vial of powder instead of several bags of plasma
Freeze-dried, reconstituted at the bedside and given over minutes. The whole point is that it is concentrated: the same clotting factors as several units of plasma in a fraction of the fluid.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
The product is lyophilised and reconstituted immediately before use. In the surgical trial, fluid overload or similar cardiac events occurred in 3% of the concentrate group against 13% of the plasma group, which is the clearest quantification of what the concentration buys.
Goldstein JN, Refaai MA, Milling TJ Jr, et al. Four-factor prothrombin complex concentrate versus plasma for rapid vitamin K antagonist reversal in patients … · a recorded source, not a stored snapshot
These are proteins the blood already contains, just not in working form. Infused, they mix straight into the plasma. Nothing has to be absorbed, converted or transported.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
Administration rapidly increases plasma levels of the vitamin-K-dependent factors II, VII, IX and X together with proteins C and S. Measured factor levels were higher in the concentrate arm than the plasma arm from 0.5 to 3 hours after infusion start (p<0.02).
Goldstein JN, Refaai MA, Milling TJ Jr, et al. Four-factor prothrombin complex concentrate versus plasma for rapid vitamin K antagonist reversal in patients … · a recorded source, not a stored snapshot
All four factors carry a special calcium-binding tail. That tail is what warfarin stops the liver from building, and it is what lets the factors stick to the site of an injury rather than clotting the whole bloodstream.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
The gamma-carboxyglutamic acid domain, made by the vitamin-K-dependent carboxylase that warfarin inhibits, binds calcium and through it the anionic phospholipid exposed on damaged membranes and activated platelets. The same domain is what the manufacturing process uses to capture all four factors together on an anion exchanger.
Goldstein JN, Refaai MA, Milling TJ Jr, et al. Four-factor prothrombin complex concentrate versus plasma for rapid vitamin K antagonist reversal in patients … · a recorded source, not a stored snapshot
With the finished factors present, the chain of reactions that ends in a clot can proceed. Thrombin appears, fibrinogen becomes fibrin, and the bleeding site is sealed.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Factor Xa assembled with factor Va on a phospholipid surface converts prothrombin to thrombin; factor IXa with factor VIIIa amplifies factor X activation. Restoring all four zymogens at once restores the whole sequence rather than one step of it, which is why the effect appears within minutes rather than over the hours vitamin K requires.
Goldstein JN, Refaai MA, Milling TJ Jr, et al. Four-factor prothrombin complex concentrate versus plasma for rapid vitamin K antagonist reversal in patients … · a recorded source, not a stored snapshot
The INR falls — faster than the actual clotting capacity returns
The blood test comes back to normal within half an hour. That number is dominated by the shortest-lived of the four factors, so it looks better than the underlying situation and starts drifting up again as that factor clears.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
Rapid INR reduction to 1.3 or below at 0.5 hours in 62.2% against 9.6% on plasma in major bleeding, and 55% against 10% before urgent surgery. Factor VII has a plasma half-life of a few hours against days for factor II, so the INR reports the arrival and departure of factor VII more than the durable haemostatic state. Vitamin K is given alongside in every protocol for exactly this reason.
Goldstein JN, Refaai MA, Milling TJ Jr, et al. Four-factor prothrombin complex concentrate versus plasma for rapid vitamin K antagonist reversal in patients … · a recorded source, not a stored snapshot
Bleeding was controlled about as well as with plasma, or better before surgery, and much faster. Neither trial was built to find out whether that means fewer deaths, and no trial since has been either.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
Effective haemostasis 72.4% against 65.4% in major bleeding (difference 7.1%, 95% CI -5.8 to 19.9) and 90% against 75% before urgent surgery (difference 14.3%, 95% CI 2.8 to 25.8). Deaths were reported as a safety outcome and were similar between arms in trials of 202 and 181 patients, which excludes essentially nothing.
Goldstein JN, Refaai MA, Milling TJ Jr, et al. Four-factor prothrombin complex concentrate versus plasma for rapid vitamin K antagonist reversal in patients … · a recorded source, not a stored snapshot
No suggested links are held for this record, so nothing is hidden from this path.
What we know
The record describes 6 steps from taking it to an effect in a person.
How we know it
Each step names the study behind it in the technical detail beside it.
What this does not prove
A change inside the body is a reason to look. It is not a result in a person.
Why it matters
A reader can see exactly where the chain stops being measured in people.
What we still do not know
No reviewed claim binds any of these steps to a named population.
What is missing or unclear◇Read from sources, not yet reviewed
Were people like you studied?
RNAWiki cannot tell whether a study fits you. It can show who was in it, and where the result stops carrying.
Who was studied
People similar to this profile were included.
Adults on warfarin who arrive with major bleeding — most often into the brain or the gut — or who need an operation that cannot wait. Very large amounts of its actual use are off-label, for bleeding on drugs it has never been licensed to reverse.
Who is missing from the studies
Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
Where the result stopped carrying
PROCOAG found no reduction in blood product consumption in trauma and a 48% relative increase in thromboembolic events
Both licensing trials were open-label with adjudicated haemostatic endpoints and manufacturer funding, and neither was powered for any clinical outcome
In the only randomised comparison against a specific antidote, the concentrate achieved haemostatic efficacy in 53.1% against 67.0%
This is a scope explorer, not a diagnosis engine.
It shows who was studied so you can see whether people similar to you were included.
RNAWiki cannot tell whether a study fits you. It can show who was in it.
What it would be like to take◇Read from sources, not yet reviewed
Why it might seem to do nothing
A real effect and a noticed effect are different things. These are the recorded reasons the two come apart.
It was studied in different people
The people in the studies were not much like the reader.
On this record: Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
The evidence may simply be wrong
Small early studies often do not hold up.
On this record: RNAWiki has not yet published a reviewed conclusion for this use.
Other reasons RNAWiki checked and found nothing for (11)
It was studied for a different goal
The studies measured something else entirely. Nothing in this record points to this reason.
A different form was studied
The studied form is not the form on the shelf. Nothing in this record points to this reason.
There was nothing to correct
Where a level is already normal, topping it up may change nothing. Nothing in this record points to this reason.
Something else had to happen too
In the studies it was paired with training, a diet or another treatment. Nothing in this record points to this reason.
The change is too small to feel
A real change can still sit below what a person notices. Nothing in this record points to this reason.
Day-to-day swing hides it
Sleep, food, stress and time of day move most numbers more than this would. Nothing in this record points to this reason.
Not enough time yet
The studies ran longer than the person has waited. Nothing in this record points to this reason.
It was not taken as studied
Missed days change the result, and studies count them. Nothing in this record points to this reason.
Something else changed at the same time
Two changes at once cannot be told apart afterwards. Nothing in this record points to this reason.
The product may not be what it says
Contents of a sold product are not always what the label states. Nothing in this record points to this reason.
No recorded reason
RNAWiki has nothing stored that would explain it. Nothing in this record points to this reason.
None of these is a reason to take more. Taking more is not a step this page ever suggests.
What it would be like to take◇Read from sources, not yet reviewed
What taking it involves
The recorded facts about getting hold of it and using it. Nothing here is a suggestion about what you should do.
How it is supplied
Given by a clinician
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Read from the recorded approval status.
No source is stored against this line.
Form and route
Intravenous infusion of a reconstituted lyophilised concentrate, given once
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form and route recorded on this substance.
No source is stored against this line.
Who oversees it
RNAWiki has not recorded a supervision or regulatory status for this substance.
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
No register row and no identity class settled the question.
No source is stored against this line.
What is in the pack
Supplied as a freeze-dried powder with diluent, reconstituted at the bedside and infused over minutes. Vitamin K is given alongside it in every protocol, because the concentrate covers only the hours until the liver resumes making its own factors. There is no other route.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on how this is sold and what that means for what is in the pack.
No source is stored against this line.
Where it is registered
Not recorded.
∅ Nothing recorded
Where this came from
RNAWiki holds nothing here and says so rather than guessing.
No register entry is recorded.
No source is stored against this line.
Why people stop
Not recorded.
∅ Nothing recorded
Where this came from
RNAWiki holds nothing here and says so rather than guessing.
No record of why people stopped taking it is stored for this substance.
No source is stored against this line.
What it would be like to take◇Read from sources, not yet reviewed
What can go wrong
Sorted by where each line came from. A regulator's label and a report somebody sent in are not the same kind of fact.
·Worth asking a clinician aboutWritten into the record from the studies named on this page
Carries a boxed warning stating that patients on vitamin K antagonist therapy have underlying disease states predisposing them to thromboembolic events, and that both fatal and non-fatal arterial and venous thromboembolic complications have been reported in clinical trials and postmarketing surveillance. The product is plasma-derived, so it carries the residual theoretical risk of transmissible agents despite pasteurisation at 60°C for 10 hours, calcium phosphate adsorption and virus filtration. It contains heparin and is therefore contraindicated where heparin-induced thrombocytopenia is suspected. Thromboembolic event rates were similar to plasma in the elderly warfarin populations of the licensing trials and markedly higher than placebo in the trauma population of PROCOAG.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
Goldstein JN, Refaai MA, Milling TJ Jr, et al. Four-factor prothrombin complex concentrate versus plasma for rapid vitamin K antagonist reversal in patients … · a recorded source, not a stored snapshot
Over a long time. No completed tested study window is recorded, so long-term effects are not established by the registry record.
Groups the studies covered thinly. Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What is missing or unclear◇Read from sources, not yet reviewed
Does the exact form matter?
Evidence belongs to the exact thing that was tested. A different salt, a different mixture or a different preparation is a different question.
The form that was studied
Intravenous infusion of a reconstituted lyophilised concentrate, given once
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form used in the studies cited on this page.
No source is stored against this line.
What is sold
Vitamin K is given alongside it in every protocol, because the concentrate covers only the hours until the liver resumes making its own factors. There is no other route.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on which forms are sold and how they compare.
No source is stored against this line.
What is recorded as being sold
12816 marketed supplement labels list this ingredient, classed as botanical, botanical with nutrients, non-nutrient/non-botanical and other combinations.
Those labels carry all other, nutrient and structure/function claims. A claim of that kind is written by the manufacturer and is not assessed by any regulator, so its presence says nothing about whether it is true.
Evidence carries across two names for one substance. It does not carry across a salt, a mirror form or a mixture.
What it would be like to take◇Read from sources, not yet reviewed
What you could measure
This one is decided with a clinician, so this section holds questions to ask rather than a plan to run.
RNAWiki could not confidently classify this substance, so no self-experiment plan is offered.
Questions worth asking
Which of the trials of Four-Factor Prothrombin Complex Concentrate studied people like me?
What was measured, and for how long?
Was the result a laboratory value or a health outcome?
What would we watch for, and when would we stop?
Tracking can show whether something changed for you. It cannot show what caused it.
RNAWiki records evidence. It does not say whether this substance is right for you.
What is missing or unclear◇Read from sources, not yet reviewed
Claims that go past the evidence
Things said about this substance that sound reasonable, and the exact step that is missing between the evidence and the claim.
✗Goes past the evidence
That faster INR correction than plasma means fewer deaths — never compared, in thirteen years on the United States market
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That an INR of 1.3 at thirty minutes represents restored haemostatic capacity, when the INR is dominated by the shortest-lived factor in the product
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That replacing clotting factors reverses a direct oral anticoagulant that is still present and still blocking factor Xa — the mechanism is different from warfarin reversal, and the practice is entirely off-label
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That the thromboembolic safety seen in elderly warfarin patients transfers to a young trauma population; PROCOAG says it does not
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
What is missing or unclear◇Read from sources, not yet reviewed
What nobody knows yet
Open questions, each with why it is open and what would close it.
How much did people take in the studies?
The sources RNAWiki checked hold nothing for this field.
Why it matters. A result belongs to an amount. Without the amount the result floats free.
What would answer it
A stored source that records it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing populations
Which groups were under-represented in the studies has not been recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing long-term data
No completed tested study window is recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
No reviewed conclusion
RNAWiki has not yet published a reviewed conclusion for this use.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing interaction studies
No interaction was found in the registers checked. Not finding one is not the same as showing there is none.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Formulation uncertainty
Several salts, forms or products of Four-Factor Prothrombin Complex Concentrate are recorded. Results from one form may not transfer to another.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Mechanism not reviewed
No reviewed mechanism story exists for this substance.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
What happened in people◇Read from sources, not yet reviewed
Check any of this yourself
Every line above traced back to the study it came from. This is the technical layer, and the vocabulary changes here.
Every line above can be traced to the study named beside it. Follow the link and read it.
It corrects the INR six times as often as plasma does
In plain words
In warfarin patients with major bleeding, the INR came down to 1.3 or below within half an hour in 62.2% of those given the concentrate against 9.6% of those given plasma. Bleeding control was similar in both groups.
What was measured
Twenty-four-hour effective haemostasis and INR correction to 1.3 or below at 0.5 hours after infusion
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Sarode et al. ran a phase 3b, multicentre, open-label, non-inferiority trial in non-surgical patients on vitamin K antagonists presenting with major bleeding. The intention-to-treat efficacy population was 202 patients (98 concentrate, 104 plasma), median baseline INR 3.90 and 3.60. Effective haemostasis over 24 hours was achieved in 72.4% against 65.4%, meeting non-inferiority (difference 7.1%, 95% CI -5.8 to 19.9). Rapid INR reduction to 1.3 or below at 0.5 hours was achieved in 62.2% against 9.6%, meeting superiority (difference 52.6%, 95% CI 39.4 to 65.9). Measured coagulation factor levels were higher in the concentrate group from 0.5 to 3 hours after infusion. Adverse events, serious adverse events, thromboembolic events and deaths were similar between groups.
Written into the record, not signed off as a reviewed claim
Before urgent surgery it beat plasma on bleeding as well as on the blood test
In plain words
In 181 patients needing an operation within hours, effective haemostasis was achieved in 90% on the concentrate against 75% on plasma. Fluid overload happened in 3% against 13%.
What was measured
Effective haemostasis and rapid INR reduction before an urgent surgical or invasive procedure
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Goldstein et al. randomised 181 vitamin-K-antagonist-treated patients needing rapid reversal before an urgent surgical or invasive procedure, with vitamin K given to both arms. In the 168-patient intention-to-treat efficacy population, effective haemostasis was achieved in 78 of 87 (90%) on concentrate against 61 of 81 (75%) on plasma, demonstrating both non-inferiority and superiority (difference 14.3%, 95% CI 2.8 to 25.8). Rapid INR reduction was achieved in 55% against 10% (difference 45.3%, 95% CI 31.9 to 56.4). Thromboembolic adverse events occurred in 7% against 8%, fluid overload or similar cardiac events in 3% against 13%, and late bleeding in 3% against 5%. The trial was funded by CSL Behring and was open-label, which matters for an endpoint adjudicated as effective haemostasis.
Written into the record, not signed off as a reviewed claim
Thirteen years on the United States market and no mortality comparison
In plain words
Neither licensing trial was designed to find out whether patients given the concentrate were more likely to survive than patients given plasma. Neither was any trial since.
What was measured
That correcting the INR six times faster than plasma translates into fewer deaths — the reason the drug is stocked, and a comparison that has never been made
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Both pivotal trials were non-inferiority studies with co-primary endpoints of adjudicated haemostatic efficacy and INR correction, in 202 and 181 patients respectively. Deaths were reported as a safety outcome and were similar between arms, which at those sample sizes excludes almost nothing. The INR itself is a problematic surrogate here for a specific reason: it is dominated by factor VII, which has a half-life of a few hours, while factor II persists for days. An INR of 1.3 at thirty minutes therefore reports the arrival of the shortest-lived factor in the bottle rather than the durable restoration of haemostatic capacity, and the same INR can be reached with quite different amounts of underlying thrombin generation.
Written into the record, not signed off as a reviewed claim
In trauma it saved no blood products and caused more clots
In plain words
A blinded French trial gave the concentrate or saline to 324 badly injured patients at risk of massive transfusion. Blood product use was identical. Thromboembolic events happened in 35% of the treated group against 24% of the placebo group.
What was measured
Twenty-four-hour total blood product consumption, and incidence of arterial or venous thromboembolic events
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
PROCOAG was a double-blind, randomised, placebo-controlled superiority trial at 12 French level I trauma centres from December 2017 to August 2021. Of 4,313 patients with the highest trauma activation, 327 were randomised and 324 analysed (164 concentrate, 160 placebo). Median Injury Severity Score was 36, median admission lactate 4.6 mmol/L, and 59% had a prehospital systolic pressure below 90 mmHg. Median 24-hour total blood product consumption was 12 units against 11 units, absolute difference 0.2 units (95% CI -2.99 to 3.33, p=0.72). At least one thromboembolic event occurred in 56 patients (35%) against 37 (24%), absolute difference 11% (95% CI 1% to 21%), relative risk 1.48 (95% CI 1.04 to 2.10, p=0.03). The authors conclude the findings do not support systematic use in patients at risk of massive transfusion.
Written into the record, not signed off as a reviewed claim
It became the default reversal agent for drugs it was never tested against
In plain words
The licence covers warfarin. Most of the direct oral anticoagulants now in use have no licensed reversal agent stocked in most hospitals, so this concentrate is given instead — an entirely off-label practice that has become standard care.
What was measured
That replacing clotting factors will reverse an anticoagulant that is still circulating and still blocking factor Xa — a mechanistically different proposition from replacing factors warfarin prevented the liver from making
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
In ANNEXA-I, the randomised trial of andexanet alfa in factor-Xa-inhibitor-associated intracerebral haemorrhage, 85.5% of the 267 patients in the usual-care arm received prothrombin complex concentrate. That trial is therefore the largest controlled dataset in existence on this product for direct oral anticoagulant reversal, and it exists only because the concentrate was the control. In it, usual care achieved haemostatic efficacy in 53.1% against 67.0% for andexanet, with thrombotic events in 5.6% against 10.3% and no appreciable difference in modified Rankin score or 30-day death. The concentrate is inferior on the surrogate, better on thrombosis, and indistinguishable on outcome — which is not the result either side of the argument wanted.
Written into the record, not signed off as a reviewed claim
The boxed warning names the risk the product is built to contain
In plain words
Injecting a bolus of clotting factors into someone whose blood was deliberately thinned causes clots in some of them. The label says both fatal and non-fatal arterial and venous thromboembolic complications have been reported.
What was measured
Thromboembolic event rates across the licensing trials and the trauma trial
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The Kcentra boxed warning states that patients on vitamin K antagonist therapy have underlying disease states predisposing them to thromboembolic events, and that both fatal and non-fatal arterial and venous thromboembolic complications have been reported with Kcentra in clinical trials and postmarketing surveillance. The formulation is designed around that risk: the antithrombotic proteins C and S are deliberately retained in the product rather than purified away, and heparin is included. In the two licensing trials thromboembolic event rates were similar to plasma, 7% against 8% in the surgical trial. In PROCOAG, in a trauma population, they were 35% against 24% on placebo. The same product, the same dose scheme, and a risk that depends almost entirely on who is receiving it.
Source
KCENTRA (Prothrombin Complex Concentrate, Human) prescribing information, boxed warning and Description; DailyMed SPL set id eee1afb8-324c-42e4-8bf0-f0c9da5e6d42
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A concentrate of the four clotting factors warfarin switches off, licensed in 2013 on two open-label trials that showed it corrects the INR six times as often as plasma and stops bleeding about as well — a genuine advance in speed and fluid volume that has never been shown to save a life, and which is now given far more often for anticoagulants it was never tested against than for the one it was.
Recorded evidence blocks (3)
Q1
2 registered trials of Four-Factor Prothrombin Complex Concentrate — at which phases?
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