Expert consensus on the diagnosis and treatment of acute hemorrhagic coagulopathy

Acute hemorrhagic coagulopathy refers to a pathophysiological state
in which the ability of blood to coagulate is acutely impaired.
Bleeding is the most common clinical manifestation, but it can also present only with abnormal coagulation indicators without bleeding
.
Due to the complex mechanism of hemostasis, thrombosis
may co-exist in some cases.
Acute hemorrhagic coagulopathy, thrombocytopenia, oral anticoagulants, sepsis, acute poisoning, liver damage, severe trauma, etc.
can all cause acute hemorrhagic coagulopathy, which is common in emergency and intensive care units (ICUs), often leading to serious clinical consequences that require a timely and correct diagnosis and appropriate treatment
by clinicians.
At present, there is still a lack of high-quality clinical evidence guidance for the treatment of coagulation dysfunction in critically ill patients, and there is no unified diagnosis and treatment standard, which brings challenges
to clinical work.
Therefore, this consensus aims to formulate an expert consensus on the diagnosis and treatment of acute hemorrhagic coagulopathy by reviewing relevant literature and guidelines and integrating expert opinions, which does not involve the diagnosis and treatment
of acute thrombotic diseases and traumatic coagulopathy.

Common causes and mechanisms

Expert opinion 1 Acute hemorrhagic coagulopathy is common in the emergency department and ICU, and timely diagnosis and analysis of the cause
are required.
1 Thrombocytopenia Thrombocytopenia activates to form platelet emboli, which is the initiation step of the hemostasis process, and thrombocytopenia caused by various causes may cause coagulation dysfunction
.
A platelet count of < 100× 109 L-1 is currently defined as thrombocytopenia
.
The causes of thrombocytopenia include primary diseases of the blood system, drugs, poisons, infections, immunity, bleeding, mechanical damage, abnormal distribution, etc
.
The risk of bleeding increases
markedly when the platelet count is < 50× 109 L-1.
In acute and critically ill patients, thrombocytopenia is quite common, and studies have calculated that 14% ~ 44% of patients admitted to the ICU have thrombocytopenia during treatment
.

2 Coagulopathy caused by oral anticoagulants

Oral anticoagulants are a common cause
of acute coagulopathy.
As the incidence of thromboembolic disease increases, oral anticoagulants are becoming more widely used, and a European study showed that oral anticoagulants were used in 9% of emergency patients
.
Commonly used oral anticoagulants include vitamin K antagonist (VKA) and direct oralanticoagulant (DOAC).

。 VKA (such as warfarin) exerts anticoagulant effect by inhibiting the synthesis of vitamin K-dependent coagulation factors II.
, VII.
, IX.
, X.
; DOACs mainly include factor II.
a inhibitors (such as dabigatran) and factor Xa inhibitors (rivaroxaban, apixaban), which exert anticoagulant effects
by directly inhibiting the activity of corresponding coagulation factors.
There is a bleeding risk with oral anticoagulants, and the risk of bleeding with warfarin to prevent thrombosis in atrial fibrillation is about 1.
0 ~ 3.
8% / person · The risk of massive bleeding in the treatment of deep vein thromboembolism by DOAC is about 1.
2 ~ 2.
2%/(person· year).

3 Coagulopathy due to sepsis

There is a strong link between immunity and coagulation, with inflammation and associated coagulation system abnormalities being the main mechanisms
of sepsis.
Coagulopathy in patients with sepsis can lead to disseminated intravascular coagulation (DIC), which can occur
before the coagulation disorder progresses to dominant DIC in patients with sepsis 。 Studies have shown that approximately 30% of patients with sepsis can have DIC, resulting in multiple organ dysfunction syndrome (MODS
).
In 2017, the International Society for Thrombosis and Hemostasis proposed the use of the term "sepsis-induced coagulopathy (SIC)" to describe this pre-DIC change
in coagulation 。 The mechanism of its occurrence may include:(1) release of damage-related molecular patterns: sepsis can induce cell damage and death, thereby releasing intracellular components such as histones, chromosomal DNA, mitochondrial DNA, nucleosomes, high-mobility group proteins B1, and heat shock proteins, activating the coagulation system and inducing DIC development; (2) Formation of neutrophil extracellular traps (NETs): NETs are components synthesized and released by neutrophils to fight pathogenic microorganisms, which themselves have the ability to activate factor XII, and can also regulate thrombin synthesis
mediated by factor VII a pathway by releasing extracellular tissue factors 。 In addition, NETs can also stimulate neutrophils to adsorb activated platelets, resulting in thrombocytopenia; (3) Glycocalyx and endothelial cell destruction: The glycocalyx covered by the endothelial surface of the blood vessel has important anticoagulant activity, in the case of inflammation, oxygen free radicals, heparanase and other proteases can destroy the glycocalyx, so that the endothelium occurs glycocalyx shedding, thereby exposing the E-selectin and adhesion molecules on the endothelial surface, so that it recruits platelets and neutrophils and promotes thrombosis
.

4 Coagulation dysfunction due to acute poisoning

Drug poisoning often leads to acute coagulation dysfunction, of which anticoagulant rodenticides are more common
.
At present, the anticoagulant rodenticides used in China mainly include 6 kinds of warfarin, rodenticide, bromidon, dalon, dichlorfen and chlordichlorin, all of which are vitamin K antagonists
.
Other poisonings such as snakebites, edible mushrooms, etc.
can also cause coagulation dysfunction
.

5 Coagulopathy due to liver damage

Patients with liver impairment are often associated with one or more coagulation dysfunctions :(1) Coagulation factor deficiency: The liver is the site of synthesis of most coagulation factors, including fibrinogen (factor I.
), thrombin (factor II.
), and coagulation factors V.
, VII.
, IX.
, X.
, and XI.

Hepatocytes are also responsible for post-translational modifications of coagulation factors, such as glycosylation and γ-carboxylation
of some factors.
The synthesis and post-translational modification of coagulation factors in patients with liver function impairment may be impaired, affecting the plasma concentration and function of coagulation factors; (2) Thrombocytopenia and platelet dysfunction: There are different degrees of reduction in platelet count in patients with liver function impairment, and the mechanism is that the decrease in thrombopoietin synthesized by the liver affects platelet production, increased splenic isolation of platelets during portal hypertension and hypersplenism, and bone marrow suppression caused by hepatitis C virus infection, alcohol consumption, other infections, or antiviral therapy; (3) Hyperfibrinolysis: The rate of fibrinolysis in patients with liver function impairment is usually accelerated, and the mechanism is that the level of tissue plasminogen activator (tPA) leads to the enhancement of plasmin production, the α of 2-antiplasmin and coagulation factor X.
III.
, and the level of fibrinolytic inhibitors activated by thrombin, and the increase of fibrin degradation products interferes with normal hemostasis
.
6 DIC

DIC is the intermediate link of the complex pathophysiological process of a variety of diseases, and its common underlying diseases or triggers include: sepsis, malignant tumors, trauma, surgery, amniotic fluid embolism, intravascular hemolysis, etc.
, which can lead to a large number of procoagulant substances appearing in the circulating blood in a short time, causing extensive thrombosis in the blood vessels, and
then causing coagulation factor depletion and large-scale activation of the fibrinolytic system, resulting in an increase in fibrin degradation products.
Obstructs normal fibrin polymerization and fibrinogen binding to platelets, interferes with fibrin clot formation and platelet aggregation, and causes secondary bleeding tendency
.

7 Hereditary or/and acquired coagulopathy

Refers to a deficiency
of coagulation factors caused by hereditary factors or other diseases caused by the body's production of antibodies to coagulation factors.
Coagulation factor deficiency caused by genetic factors often has a positive family history, and some non-genetic factors have clinical manifestations
of other diseases.

Expert opinion on coagulation assessment 2 recommends screening with routine blood tests first
.

1 Platelet count and blood smear for broken red blood cell platelet count and blood smear for broken red blood cells are routine tests and are very important
for the identification and management of acute coagulation disorders.
When platelets are progressively declined, be alert to the occurrence
of DIC in addition to considering immune-mediated thrombocytopenia and myelosuppression.
Red blood cells are the most abundant cells in the peripheral blood smear, broken red blood cells are red blood cell fragments or incomplete red blood cells, and less than 1%
of broken red blood cells in normal peripheral blood.
Fragmentation of erythrocytosis is common in thrombotic microangiopathy and failure
of heart implanted valves or devices.

2 Related indicators of coagulation factor consumption

Indicators of coagulation factor consumption are prothrombin time (PT), activated partial thromboplastin time (APTT), activated partialthromboplastin time, activated clotting time, activated clotting time, ACT)
。 PT measures the time it takes for plasma to clot when exposed to tissue factors and can be used to assess exogenous clotting pathways and co-coagulation pathways
.
APTT measures the time it takes for plasma to clot after exposure to a substance that activates contact factors and assesses endogenous coagulation pathways and co-coagulation pathways
.
The normal range of PT and APTT measured by different laboratories and different reagent/instrument combinations is different, and the normal range of PT in most laboratories is 11 ~ 13 s, and the normal range of APTT is 25 ~ 35 s
.
Fibrinogen is measured by the concentration of fibrinogen in plasma, and the normal range is 200 ~ 400 mg/dL
.
ACT measures the time required for whole blood (not plasma) to clot after exposure to activated contact factors, and like APTT, this test evaluates endogenous coagulation pathways and common coagulation pathways, which can determine the amount of heparin anticoagulation and protamine antagonism required in the blood, and the normal ACT range is 59.
2 ~ 117 s
.
When genetic or acquired coagulopathy is suspected, a PT, APTT mixed plasma correction test
should be performed.

3 Related indicators of fibrinolysis system activation

Relevant indicators of fibrinogen/fibrin degradation product (FDP) and D-dimer
include fibrinogen/fi brin degradation product (FDP).
FDP is a degradation product produced by plasmin acting on fibrinogen or fibrin, and its level reflects the functional status
of the fibrinolytic system.
D-dimer is a degradation product of fibrin clots that specifically reflects the fibrinolysis of cross-linked fibrin and more reliably indicates the risk of thrombosis, and plasma D-dimer levels of < 500 ng/mL are often used clinically as cut-off values
for thrombosis exclusion.

Expert opinion 3 Thromboelastography is recommended for further assessment of coagulation function
in patients with established coagulopathy.

4.
Thrombelastography (TEG)

Record the entire thrombus process, including clot formation and progression, clot retraction and dissolution, and provide information about
the thrombotic process such as thrombosis speed, strength, and
stability.
Important parameters of thromboelastography include: R time (coagulation reaction time), R<5 min for high coagulation factor activity, 5 min < R < 10 min for normal coagulation factor activity, R>10 min for low
coagulation factor activity.
K time and α angle (blood clot formation kinetic index) reflect fibrin level, K<1>72o is high fibrin level; 1 min for 3min, α<53o ma=""">70 mm for high platelet function, 50 mm3 for hypercoagulable state
.
LY30 (reflecting clot stability) refers to the percentage reduction in amplitude 30 minutes after MA, normal < 7.
5%, and an increase in LY30 indicates hyperfibrinolysis
.
EPL (predicted fibrinolysis index) refers to the expected percentage of blood clot ablation after the onset of MA, normal <15%, and elevated EPL indicates hyperfibrinolysis
.
The test items include: TEG general test (full picture of the patient's coagulation), TEG heparin test (heparin, low molecular weight heparin test), TEG platelet map (antiplatelet drug test).

TEG plays an increasingly prominent role in acute coagulation dysfunction, and can be used for qualitative analysis of coagulation factors, fibrinogen, and platelets to help determine coagulation and fibrinolytic status
.
In patients with acute coagulopathy, try to complete the TEG test
.

Expert opinion 4 For patients with complex clinical conditions, early evaluation
of novel molecular markers of thrombosis is recommended.

5 Novel molecular markers of thrombosis

2.
5.
1 After thrombin formation in vivo thrombin of thrombin antithrombin complex (TAT), part of it quickly binds to antithrombin (AT) to form thrombin antithrombin complex (TAT), which is a molecular marker reflecting thrombin production, which can sensitively reflect the degree of activation of the coagulation system and directly reflect the activation of the coagulation system
.
The half-life of thrombin in the blood is only a few seconds, which is difficult to
measure directly.
The plasma half-life of TAT is 3 ~ 15 min, which can be directly measured, and the normal plasma value of TAT is <4 tat="">4 ng/mL, indicating increased
thrombin synthesis.
Elevated TAT predicts the risk of thrombosis and recurrence early and the risk
of DIC early.

2.
5.
2 Plasmin antiplasmin complex (PIC) plasmin antiplasmin complex (PIC) is a 1:1 binding complex of plasmin to the inhibitor α 2 antiplasmin, which is a biomarker that directly reflects the degree of activation of the fibrinolytic system
.
PIC plasma half-life is about 6 h, which can be measured directly, and a normal plasma value of <0.
8 pic=""">0.
8 μ g/mL often indicates fibrinolytic system activation
.
The degree of fibrinolytic activation varies depending on the underlying DIC disease and is closely related to DIC typing, which can be used to predict hypercoagulable state early and can also be used for thrombolytic therapy monitoring
.

2.
5.
3 Tissue plasminogen activator - Plasminogen activation inhibitor -1 complex (tPAIC) When vascular endothelial cells are damaged, tissue plasminogen activator and plasminogen activation inhibitor -1 are released into the blood at the same time, and 1:1 combine to form tissue plasminogen activator-plasminogen activator-1 complex (tissue plasminogen activator-plasminogen activator).
inhibitor-1 complex, tPAIC), tPAIC can reflect endothelial cell damage, is a molecular marker of fibrinolytic system activation, positive blood plasma < 17.
0 ng/mL in men and 10.
5 ng/mL
in women< 。 tPAIC is suggestive of DIC and arteriovenous thrombosis, and is a risk indicator for vein thromboembolism (VTE) and myocardial infarction, and is of great value for the diagnosis of DIC, and elevated plasma levels suggest possible DIC, vascular endothelial cell damage, and thrombosis
.

2.
5.
4 Blood embolism regulation of egg white (TM) Thrombomodulin (TM) is the thrombin receptor on the surface of endothelial cells, inhibits the activity of thrombin, enhances the activation performance of protein C, and the normal value of plasma TM is 3.
8 ~ 13.
3 TU/mL
.
When endothelial cells are damaged or dysfunctional, TM expression is reduced and part of TM is hydrolyzed into plasma by
proteases.
Therefore, TM is a marker of endothelial cell damage
.
Elevated TM suggests vascular endothelial injury, which can be seen in sepsis, impaired renal function, and acute lung injury
.

Expert opinion on the diagnosis of acute hemorrhagic coagulopathy 5 A four-classification approach is recommended for the diagnosis
of acute hemorrhagic coagulopathy
.

At present, there are no clear and unified diagnostic criteria for acute coagulation dysfunction, and the medical history, triggers, and laboratory abnormalities are the main diagnostic basis
.
Acute coagulopathy is a pathophysiologic condition, and many disorders produce similar laboratory abnormalities
.
In order to facilitate etiological identification and disease management, Hunt divided coagulation disorders into four categories: (1) thrombocytopenia, normal coagulation function, and no broken red blood cells on the blood smear; (2) Thrombocytopenia, normal coagulation function, broken red blood cells on blood smear; (3) Thrombocytopenia, the presence of coagulation disorders; (4) Platelets are normal and there is coagulation disorder
.

The first category refers to thrombocytopenia
caused by various causes.
The second type is usually seen in thrombotic microangiopathy, such as thrombotic thrombocytopenic purpura/hemolytic uremic syndrome
.
The third category refers to diseases that cause a large depletion of clotting factors, such as DIC
.
The fourth category refers to diseases that cause decreased production of clotting factors or inhibition of clotting factors, such as liver failure and oral anticoagulants
.
Combined with the history and clinical presentation, this classification can clinically help doctors determine the cause and diagnosis
.

Expert opinion 6 recommends the ISTH DIC score for the diagnosis of DIC-related coagulopathy
.

The diagnosis of DIC requires a comprehensive evaluation
based on the patient's underlying disease, clinical manifestations, and laboratory tests.
In recent years, the International Society of Thrombosis and Hemostasis Standards (ISTH), the Japanese Ministry of Health and Welfare Standards (JMHW), the Japanese Society of Emergency Medicine Standards (JAAM), and the Chinese Society of Hematology Thrombosis and Hematology Group (CDSS) have all developed multi-index DIC scoring diagnostic systems
.
This consensus is primarily based on the ISTH DIC score (Table 1).

Pre-DIC (pre DIC) refers to the presence of some clinical manifestations and/or laboratory tests of DIC without meeting diagnostic criteria for compensatory status (score < 5).

Overt DIC refers to the patient's decompensation phase, i.
e.
, clinically typical DIC (score ≥ 5).

Sepsis-related coagulopathy (SIC) refers to infection-induced organ dysfunction and coagulopathy, and diagnosis is based on only three indicators: platelets, PT- international normalized ratio (INR), and sequental organ failure assessment (SOFA) score, which can be diagnosed by a score of ≥ 4 (Figure
。

Treatment of acute hemorrhagic coagulopathy

Expert opinion 7 Eliminate or control the cause
of coagulopathy as early as possible.

1 Treatment of etiology

Elimination or control of the underlying cause is the cornerstone of treatment of
acute coagulopathy.
When the cause is properly managed, many patients have improved coagulopathy
.
For example, for sepsis-induced coagulopathy, the use of sensitive antibiotics as soon as possible and drainage of the lesion of infection are the most important treatment measures; For bleeding caused by oral anticoagulants, prompt discontinuation or use of reversal anticoagulants can correct coagulopathy
.

Expert opinion 8 Complete the assessment of severity as soon as possible with adequate life support
.

2 Initial assessment and support

In the presence of acute coagulopathy, it is necessary to quickly complete the assessment of airway, breathing, and circulation, and give corresponding initial support; Complete the evaluation of coagulation function indicators, especially those related to coagulation factor depletion and platelet count, and decide whether to initiate replacement therapy according to the severity; Vital signs and bleeding manifestations are continuously monitored for further treatment
.

Patients with airway obstruction and loss of airway protection require prompt airway opening and endotracheal intubation to prevent aspiration and maintain adequate alveolar ventilation
.
In patients with bleeding, oxygen therapy is required to increase oxygen saturation and improve the decrease in oxygen supply due to a decrease
in hemoglobin.
Patients with hypoperfusion require fluid resuscitation to maintain hemodynamic stability and component transfusion as needed
.

3 Principles for the management of severe bleeding

In the presence of acute hemorrhagic coagulopathy, the severity of the bleeding determines the choice
of next course of treatment.
Blood transfusion and discontinuation of anticoagulation are not necessarily required
in patients with coagulopathy who have no bleeding or only minor bleeding and are not currently ready to perform invasive procedures.
When patients with coagulopathy present with massive blood loss, or significant closed body cavity bleeding (eg, intracranial hemorrhage, posterior peritoneal hemorrhage, intraorbital hemorrhage, etc.
), or active bleeding requiring surgery, intervention, or endoscopic hemostasis, these conditions are considered severe bleeding, have a fatal risk, and require aggressive intervention
.
Interventions include: discontinuation of anticoagulant or antiplatelet drugs; Consider retroverting anticoagulant therapy when severe bleeding is suspected of being caused by an anticoagulant; In the absence of contraindications, consider the use of antifibrinolytic agents ; Use alternative therapy
if necessary.

4 Drug treatment

Expert opinion 9 For bleeding patients taking oral anticoagulants, relevant reversal therapy
is recommended.

4.
4.
1 Reversal drugs of DOAC for direct oral anticoagulation are used in patients with
DOAC anticoagulation accompanied by severe bleeding.
Specific reversal agents include idasizumab and Andexanet α
.
Idaslizumab is used to specifically reverse oral direct factor IIa inhibitors (dabigatran).

The 2017 REVERSE AD study demonstrated that edasizumab could reverse the anticoagulant effect of dabigatran [34], and within 15 minutes of adamizumab 5 g administration, the anticoagulant effect was completely reversed in almost all patients, and the reversal effect was maintained for 24 h
in most patients 。 Therefore, idasizumab should only be used in patients who are confident that there is still a large amount of dabigatran in the body, and should not be used in patients with normal thrombin time (TT), and only when conservative bleeding control measures are ineffective and life-threatening or require emergency surgery
.
Andexanet α is used to specifically reverse factor X.
a inhibitors
.
It is a non-catalytically active form of factor X.
a that retains factor Xa activity
by binding to factor X.
a inhibitors by surrogate factor X.
a.
It was approved by the US FDA in 2018 for life-threatening or uncontrolled bleeding
caused by rivaroxaban or apixaban.

4.
4.
2 Vitamin K Vitamin K is an indispensable coenzyme for the synthesis of factors II, VII, IX, and X, and the process of converting glutamate residues to γ-carboxyglutamate requires vitamin K-dependent γ-glutamylcarboxylase, so these clotting factors are called vitamin K-dependent coagulants
.
Vitamin K intake and gut synthesis can be problematic when liver function is impaired, so vitamin K supplementation is reasonable
.
Warfarin is a vitamin K antagonist, and bleeding associated with it can be treated with
vitamin K.
According to the guidelines of the American College of Chest Physicians (ACCP) in 2012 and the American Society of Hematology (ASH) [35] in 2018, warfarin should be discontinued with an oral administration of 2.
5 ~ 5 mg of vitamin K
with an INR of > 10 but no bleeding.
Monitor INR daily or every other day and repeat oral vitamin K
if necessary.
When the INR drops to the therapeutic range, warfarin
is reintroduced at a reduced maintenance dose.
INR between 4.
5 ~ 10 without bleeding, warfarin is discontinued, and low-dose oral vitamin K (1 ~ 2.
5 mg)
is given or not.
INR < 4.
5 without bleeding, warfarin is discontinued or the maintenance dose is slightly reduced, and INR
is closely monitored.

Expert opinion 10 Antifibrinolytic therapy
is recommended in bleeding patients with hyperfibrinolysis if DIC is not present.

4.
4.
3 Antifibrinolytic agents tranexamic acid (TXA) and 6-aminocaproic acid (EACA) are commonly used antifibrinolytic drugs, which can adsorb to the lysine binding site of the fibrin affinity site on plasmin and plasminogen, prevent plasmin, plasminogen and fibrin from binding, thereby inhibiting fibrin decomposition
.
TXA and EACA can be used in patients with
increased fibrinolytic activity and hypofibrinogenemia.
For example, in liver failure and cirrhosis, hyperfibrinolysis occurs, tPA is upregulated, and fibrinolytic inhibitors activated by plasminogen, antiplasmin, and thrombin are downregulated
.
Studies have shown the benefits of TXA in patients with upper gastrointestinal bleeding
.
It should be noted that fibrin deposition is an important feature of DIC, and blocking fibrinolysis increases the risk of thrombotic complications, so antifibrinolytic drugs are not recommended for DIC therapy
.

Expert opinion 11 Treatment with thrombopoietin receptor agonists is recommended
for bleeding patients with myelosuppressive thrombocytopenia.

4.
4.
4 Thrombopoietin receptor agonists Thrombopoietin receptor agonist (TPO-RA) increase platelet counts by stimulating TPO receptors, and it takes several days to raise
platelet counts.
Clinical scenarios commonly used with TPO-RA include chronic immune thrombocytopenia, myelodysplastic syndromes, and chemotherapy-induced thrombocytopenia
.
Because it may exacerbate thromboembolic disease, especially in patients at risk of underlying thrombophilia, the risk of
bleeding and thrombosis needs to be carefully assessed before opting for TPO-RA therapy.

Expert opinion 12 For bleeding patients who have received antiplatelet therapy, desmopressin therapy
is recommended.

4.
4.
5 Desmopressin Desmopressin can release endothelial Willebrand factor (vWF) and factor VIII, increase platelet adhesion and aggregation, and have been used to treat patients with von Willebrand disease and platelet genetic defects
.
Desmopressin has been found to improve platelet function in patients treated with aspirin and clopidogrel, and desmopressin therapy can be used in bleeding patients who have received antiplatelet therapy
.

4.
5 Substitution Treatment

Expert opinion 13 Laboratory indicators are recommended for patients with coagulopathy and severe bleeding
.

4.
5.
1 Platelets The threshold for initiating platelet transfusion depends on the clinical condition of the patient
.
For bleeding, urgent invasive procedures, and postoperative patients, platelet transfusions are typically recommended to maintain platelet counts of > 50×109 L-1 when the platelet count is < 50× 109 L-1
.
If there is severe or central nervous system bleeding, maintain a platelet count of > 100×× 109 L-1
.
When the patient has no obvious bleeding, unless the platelet count is < 10 ~ 20× 109 L-1, platelet transfusion should be given due to the increased risk of spontaneous bleeding
.
It is important to note that platelet transfusions should be contraindicated when TTP is probable unless there is severe life-threatening bleeding
.
In the presence of heparin-induced thrombocytopenia (HIT), autoantibodies to the antiplatelet factor 4-heparin complex can cause catastrophic arterial and venous thrombosis and platelet transfusions should be contraindicated
.

4.
5.
2 New Frozen Blood Plasma New fresh frozen plasma (FFP) contains all clotting factors and other plasma proteins
.
Fresh frozen plasma and 24-hour frozen plasma plasma (PF24) can be used to treat
patients with bleeding with significantly prolonged PT or APTT (more than 2 times the upper limit of normal).
The recommended starting dose for FFP is 15 mL/kg
.
There is a lack of evidence and divergent expert opinion on the timing of initiation of blood component therapy and the choice of plasma components in liver disease and coagulopathy
.
A survey of hepatologists, hematologists, critical care specialists, and surgical specialists showed that half of the support and opposition were for whether FFP was used before liver biopsy in patients with an INR >of 1.
5
.
For coagulopathy before liver transplantation, some experts choose FFP and platelets, and some choose to use prothrombin complex concentrate (PCC) and fibrous egg leukagen
.
In the absence of a unified opinion, it is recommended that the timing
of initiation of blood component therapy be based on the presence or absence of risk
of major bleeding.
For DOAC-induced bleeding, FFP or PF24 is not recommended to reverse the anticoagulant effect
of DOAC due to lack of clinical evidence to support the efficacy of frozen plasma in reversing DOAC.
For severe warfarin-related bleeding with INR > 2, FFP (starting agent 15 ~ 30 mL/kg) can be used to reverse the warfarin effect
if PCC is not available.

4.
5.
3 Prothrombin Complex Procoagulin Complex Prothrombin Complex (PCC) includes activated prothrombin complex (aPCC) and unactivated prothrombin complex (factor 3 PCC and factor 4 PCC).

aPCC is PCC
that contains at least 1 activated clotting factor.
There is no high-quality evidence to support the use of aPCC for the treatment of DOAC-related bleeding
.
However, for dabigatran-associated bleeding, if idalizumab is not available, factor VIII.
inhibitor-bypassing activity (FEIBA) can be used at an initial dose of 50 units/kg
.
Unactivated PCC is a concentrate of coagulation factors and anticoagulants purified from plasma and contains high levels of clotting factors
.
3-factor PCC contains factors II.
, IX.
and X.
; Factor 4 PCC contains factors II, IX.
, X.
and VII.

PCC can be used to treat patients with bleeding with significantly prolonged PT or APTT (more than 2 times the upper limit of normal), especially when
volume overload is not suitable for FFP.
For example, for severe bleeding associated with warfarin with an INR > 2, a factor 4 PCC is recommended to rapidly reverse the warfarin effect
.
Dose is also determined according to INR, and patients with INR > 6 typically use 50 units/kg, and repeat PT/INR
after 30 minutes of PCC.
It should be noted that PCC lacks some important clotting factors (factor V.
) and can only partially correct coagulation disorders
.

4.
5.
4 Fibrinogen concentrate In the presence of severe hypofibrinogenemia (< 100 mg/dL), fibrinogen or cryoprecipitate can be selected to increase plasma fibrinogen levels to > 100 mg/dL
.
Early fibrinogen replacement is also a key treatment for
traumatic coagulopathy.
Exogenous sources of fibrinogen include FFP, cryoprecipitate, and fibrinogen concentrate
.
Hypofibrinogenaemia
is usually treated with cryoprecipitate and fibrinogen concentrate due to the low fibrinogen content in FFP and the high risk of transfusion-related complications.
4 FFPs and 2 bags of cryoprecipitate (15 ~ 20) provide approximately 3g of purified fibrinogen
.

4.
5.
5 Cryoprecipitate Cryoprecipitate is made from insoluble precipitate collected after FFP thaws in a 4°C water bath, also known as antihemophilic factor (AHF).

1 U cryoprecipitate is about 5 ~ 20 mL and contains most of the fibrinogen (150 mg), factor VIII (80 IU), factor X.
III.
(50 ~ 75 IU), von Willebrand factor (100 ~ 150 IU) and fibronectin
in 1U FFP.
For patients with low fibrinogen, 1U cryoprecipitate can increase plasma fibrinogen concentration by at least 7 ~ 10 mg/dL
.
If factor X.
III deficiency is present, the therapeutic dose is approximately 1 unit/10 kg
.

4.
5.
6 Bloodborne or genetically recombinant coagulation factor For patients with hereditary coagulation factor deficiency, the corresponding coagulation factor is supplemented according to the type of deficiency factor, including hematogenous and/or recombinant coagulation factor , such as hemophilia A supplementation of hemogenic coagulation factor VIII preparations or recombinant coagulation factor VIII preparations
.
In patients with acquired coagulation factor deficiency, bypass clotting factors can be supplemented
.
Human recombinant-activated coagulation factor VII is a first-line hemostatic drug for acquired hemophilia, and its recommended dose is 90 μ g/kg, intravenously once every 2 ~ 3 hours until bleeding control
.

summary

Acute coagulopathy is impaired
coagulation from a range of etiologies.
Coagulopathy can be detected by clinical presentation and laboratory tests, and novel molecular markers can help identify coagulopathy early
.
The pathogenesis of coagulopathy is different for different etiologies, and eliminating the cause is the cornerstone of the treatment of
acute coagulopathy.
Antifibrinolytic drugs, oral anticoagulant reversal drugs, and blood component therapy are commonly used treatments
.
However, in the absence of high-quality clinical evidence, treatment requires dynamic assessment and careful weighing of risks and benefits
.