-
Categories
-
Pharmaceutical Intermediates
-
Active Pharmaceutical Ingredients
-
Food Additives
- Industrial Coatings
- Agrochemicals
- Dyes and Pigments
- Surfactant
- Flavors and Fragrances
- Chemical Reagents
- Catalyst and Auxiliary
- Natural Products
- Inorganic Chemistry
-
Organic Chemistry
-
Biochemical Engineering
- Analytical Chemistry
-
Cosmetic Ingredient
- Water Treatment Chemical
-
Pharmaceutical Intermediates
Promotion
ECHEMI Mall
Wholesale
Weekly Price
Exhibition
News
-
Trade Service
*It is only for medical professionals to read for reference.
It is worth seeing! Bleeding transformation after thrombolysis has always been a difficult clinical problem.
Many clinicians become very cautious after thrombolytic patients have bleeding.
They are worried about bleeding again and will no longer easily perform thrombolytic therapy.
For this thorny issue How to deal with the situation? At the 7th Annual Conference of the Chinese Stroke Society (CSA&TISC 2021), Professor Hu Bo from Union Hospital of Tongji Medical College of Huazhong University of Science and Technology brought us the title "Evaluation and Antithrombosis of Stroke Patients Accompanied by "Bleeding Transformation" "Choice" lecture, the content includes the concept, classification, diagnosis, evaluation, treatment of bleeding transformation, let us learn together! The concept of hemorrhage transformation began in 1990.
Pessin classified the hemorrhage according to the location of hemorrhage into: post-infarction hemorrhage (H1) and cerebral parenchymal hemorrhage (PH).
According to CT imaging findings, each type is divided into two subtypes, 1 and 2
.
In 1994, Levy used the concept and definition of "symptomatic intracranial hemorrhage" for the first time in the study of intravenous thrombolysis, linking cerebral hemorrhage after recanalization of acute cerebral infarction with clinical symptoms
.
Classification of hemorrhagic transformation (1) Its clinical classification is mainly based on several cerebrovascular-related studies, including: ①NINDS study: In 1995, it was carried out by the National Institute of Neurology and Stroke in the United States and included 312 patients with 0-3 hours of disease.
Stroke patients; ②ECASS II study: The European Collaborative Stroke Study in 1998 included 407 stroke patients with onset 0-6h; ③SIST-MOST Study: The European Stroke Safety Surveillance Study in 2007 included 6483 stroke patients with onset 0-3 hours ④ECASS Ⅲ study: In 2008, 821 18-80-year-old patients with acute infarction were enrolled in Europe, and the thrombolysis time window was 3-4.
5h; ⑤IST-3 study: The third international stroke study in 2012, 3035 patients had an onset of 0-6h Stroke patients
.
According to the above studies, hemorrhage transformation is divided into symptomatic intracranial hemorrhage (Symptomatic ICH, sICH) and non-symptomatic intracranial hemorrhage (Asymptomatic ICH, aICH) (see Figure 1 for specific classification)
.
Figure 1 Clinical classification of hemorrhage transformation (2) Imaging classification of hemorrhage transformation According to the ECASS study, hemorrhage transformation has been classified by imaging (see Figure 2): ①HI-1: bleeding with small spots along the edge of the infarct with increased density Point; ②HI-2: Large fusion bleeding point in the infarct, no space-occupying effect; ③PH-1: Hematoma volume is not more than 30% of the infarct area, accompanied by slight space-occupying effect; ④PH-2: Hematoma volume Not more than 30% of the infarct area, accompanied by obvious space-occupying effect
.
Figure 2 Classification of hemorrhage transformation imaging HI-1 (A); HI-2 (B); PH-1 (C); PH-2 (D) (three) Classification of cerebral hemorrhage in vascular recanalization 2015, cerebral infarction Heidelberg classification (HBC) of cerebral hemorrhage after treatment, according to the classification of imaging examination: ① hemorrhage transformation (1a, 1b, 1c); ② intracerebral hemorrhage confined to the infarcted area; ③ hemorrhage of the brain parenchymal outside the infarcted area Or intracranial-extracranial hemorrhage type three (3a, 3b, 3c, 3d)
.
(4) When is the bleeding time after thrombolysis? Secondary intracranial hemorrhage after thrombolysis mostly occurs within 4 hours after thrombolytic therapy; ECASS III study shows that SICH mostly occurs within 36 hours, and the possibility of secondary bleeding after thrombolysis is extremely low; the incidence of spontaneous hemorrhage conversion is 5%
.
7 steps for diagnosis of hemorrhage transformation 1.
Re-examination of imaging at 48 hours after treatment, and re-examination of imaging according to clinical cerebral hemorrhage; 2.
Imaging judgments are judged by independent personnel using blind methods; 3.
Cerebral hemorrhage is described according to anatomical parts; 4.
Distinguish between symptomatic intracerebral hemorrhage (sICH) and asymptomatic intracerebral hemorrhage (aICH); 5.
Determine the clinical symptom deterioration and imaging correlation, divided into: certain, very likely, possible, impossible; 6.
Among them, "definite" And “probably” are reported as sICH, and “probably” or “impossible” are reported as aICH; 7.
Determine the correlation between cerebral hemorrhage and intervention treatment: it occurs within 24 hours after intravenous or arterial thrombolysis; cerebral hemorrhage occurs in Endovascular treatment of brain areas; complications related to angiography
.
Among them, the correlation is also divided into four types: certain, probable, possible, and impossible
.
The impact of bleeding after intravenous thrombolysis on the prognosis (1) Symptomatic hemorrhage transformation (sICH) NINDS: mortality rate is 45%; PH-2: ECASS study shows that the long-term prognosis of patients is unfavorable; PH-1: ECASS study shows Only affect the short-term prognosis; HT-1: ECASSII study showed a good outcome
.
(2) Asymptomatic transformation of bleeding (aICH) NINDS, ECASSII, Atiantis A and B Trials showed no effect on the prognosis of 3 months
.
What are the risk factors for hemorrhage transformation after intravenous thrombolysis? The meta-analysis included 55 intravenous thrombolysis risk factor studies (n=65264) showing that age, high NIHSS score, and high blood sugar were independent risk factors for hemorrhage transformation; the meta-analysis included 14 intravenous thrombolysis risk factor studies of Chinese people (n =2548) showed that: age, atrial fibrillation, history of stroke, history of taking antiplatelet drugs, higher NIHSS score, blood pressure, and blood sugar levels are independent risk factors for hemorrhage transformation after thrombolysis; meta-analysis included 11 studies (n=7194 ) Showed that leukoaraiosis is an independent predictor of sICH; 8 studies (n=2601) included in the meta-analysis showed that more than 10 cerebral microhemorrhage foci may have an impact on hemorrhage transformation (see Figure 3 for a summary)
.
Figure 3 Risk factors for hemorrhage transformation after rt-PA thrombolysis.
Predictive score of hemorrhage transformation after thrombolysis.
Hemorrhage after thrombolysis (HAT) score is a practical, fast and easy-to-operate scoring standard: baseline blood pressure, NIHSS score, CT scan The infarct size can be used for reasonable risk stratification of cerebral hemorrhage after thrombolysis; SEDAN score (0-6 points): baseline blood glucose, CT scan at early admission, age, NIHSS score at admission (≥10 points, score=1), Signs of infarction (yes = 1 point), (high) density cerebral artery signs (yes = 1)
.
The absolute risk of sICH in the derived cohort was scored from 0 to 5, and the corresponding risks were 1.
4%, 2.
9%, 8.
5%, 12.
2%, 21.
7%, and 33.
3%
.
How to prevent cerebral hemorrhage transformation after thrombolysis? Hematology examination: coagulation function, blood routine, platelet count, liver function, kidney function, blood sugar; evaluation of severity of illness: NIHSS score> 25 points or coma; dose not exceeding 0.
9 mg/kg; weighing and accurately calculating the required dose ; Antiplatelet drugs and anticoagulant drugs are not used within 24 hours after thrombolysis
.
Choosing rt-PA as a thrombolytic drug: Relative fibrinolytic specificity: short half-life and fast metabolism; multiple RCTs are widely confirmed, safe and reliable; grasp the treatment time window: 4.
5h (the sooner the better); control blood pressure: SBP>185mmHg , DBP>110mmHg is contraindicated; control hyperglycemia: blood sugar <2.
7mmol/l or>22.
2mmol/l is contraindicated
.
The mechanism of hemorrhage transformation after thrombolysis is related to the structure of rt-PA itself: rt-PA has enzymatic activity, which effectively activates thrombolytic plasminogen as plasmin, and exerts thrombolytic function; rt-PA is retained after thrombolysis The blood-brain barrier (BBB) and its multi-target effects increase the risk of hemorrhage transformation after thrombolysis; reperfusion injury: the incidence of cerebral infarction hemorrhage transformation is significantly positively correlated with the recanalization time; prolonged ischemia time causes a series of complex waterfalls The cascade reaction destroys the BBB, causing harmful components of the blood to penetrate into the brain tissue, forming a vicious circle; BBB permeability increases: animal studies have confirmed that rt-PA can activate PDGF-CC, damage the integrity of BBB, and lead to hemorrhagic transformation
.
The mechanism of hemorrhage transformation after thrombolysis may provide us with corresponding targets for studying the intervention of hemorrhage transformation after thrombolysis, such as: focusing on the mechanism of rt-PA aggravating the destruction of the blood-brain barrier, MMP inhibitors, free radical scavengers, inflammation inhibitors
.
How to choose antithrombotic therapy after thrombolytic bleeding? Chinese and foreign guidelines unanimously recommend anti-platelet therapy with aspirin for most patients in the acute phase; domestic and foreign guidelines recommend dual antiplatelet therapy for high-risk TIA and early ischemic stroke; aspirin is the common recommendation of domestic and foreign guidelines for long-term antithrombotic therapy; domestic Foreign guidelines/consensus recommend that patients with cerebral hemorrhage should resume antithrombotic therapy in time if they have antithrombotic indications, and the timing needs to be individualized; Chinese expert consensus on dual antiplatelet therapy for coronary heart disease (2021): high bleeding risk of receiving dual antibodies Patients should continue to use or resume aspirin treatment.
After gastrointestinal bleeding occurs, it is necessary to decide to continue using the original anti-platelet regimen, or continue taking/resuming aspirin in time based on the risk of rebleeding
.
It is worth seeing! Bleeding transformation after thrombolysis has always been a difficult clinical problem.
Many clinicians become very cautious after thrombolytic patients have bleeding.
They are worried about bleeding again and will no longer easily perform thrombolytic therapy.
For this thorny issue How to deal with the situation? At the 7th Annual Conference of the Chinese Stroke Society (CSA&TISC 2021), Professor Hu Bo from Union Hospital of Tongji Medical College of Huazhong University of Science and Technology brought us the title "Evaluation and Antithrombosis of Stroke Patients Accompanied by "Bleeding Transformation" "Choice" lecture, the content includes the concept, classification, diagnosis, evaluation, treatment of bleeding transformation, let us learn together! The concept of hemorrhage transformation began in 1990.
Pessin classified the hemorrhage according to the location of hemorrhage into: post-infarction hemorrhage (H1) and cerebral parenchymal hemorrhage (PH).
According to CT imaging findings, each type is divided into two subtypes, 1 and 2
.
In 1994, Levy used the concept and definition of "symptomatic intracranial hemorrhage" for the first time in the study of intravenous thrombolysis, linking cerebral hemorrhage after recanalization of acute cerebral infarction with clinical symptoms
.
Classification of hemorrhagic transformation (1) Its clinical classification is mainly based on several cerebrovascular-related studies, including: ①NINDS study: In 1995, it was carried out by the National Institute of Neurology and Stroke in the United States and included 312 patients with 0-3 hours of disease.
Stroke patients; ②ECASS II study: The European Collaborative Stroke Study in 1998 included 407 stroke patients with onset 0-6h; ③SIST-MOST Study: The European Stroke Safety Surveillance Study in 2007 included 6483 stroke patients with onset 0-3 hours ④ECASS Ⅲ study: In 2008, 821 18-80-year-old patients with acute infarction were enrolled in Europe, and the thrombolysis time window was 3-4.
5h; ⑤IST-3 study: The third international stroke study in 2012, 3035 patients had an onset of 0-6h Stroke patients
.
According to the above studies, hemorrhage transformation is divided into symptomatic intracranial hemorrhage (Symptomatic ICH, sICH) and non-symptomatic intracranial hemorrhage (Asymptomatic ICH, aICH) (see Figure 1 for specific classification)
.
Figure 1 Clinical classification of hemorrhage transformation (2) Imaging classification of hemorrhage transformation According to the ECASS study, hemorrhage transformation has been classified by imaging (see Figure 2): ①HI-1: bleeding with small spots along the edge of the infarct with increased density Point; ②HI-2: Large fusion bleeding point in the infarct, no space-occupying effect; ③PH-1: Hematoma volume is not more than 30% of the infarct area, accompanied by slight space-occupying effect; ④PH-2: Hematoma volume Not more than 30% of the infarct area, accompanied by obvious space-occupying effect
.
Figure 2 Classification of hemorrhage transformation imaging HI-1 (A); HI-2 (B); PH-1 (C); PH-2 (D) (three) Classification of cerebral hemorrhage in vascular recanalization 2015, cerebral infarction Heidelberg classification (HBC) of cerebral hemorrhage after treatment, according to the classification of imaging examination: ① hemorrhage transformation (1a, 1b, 1c); ② intracerebral hemorrhage confined to the infarcted area; ③ hemorrhage of the brain parenchymal outside the infarcted area Or intracranial-extracranial hemorrhage type three (3a, 3b, 3c, 3d)
.
(4) When is the bleeding time after thrombolysis? Secondary intracranial hemorrhage after thrombolysis mostly occurs within 4 hours after thrombolytic therapy; ECASS III study shows that SICH mostly occurs within 36 hours, and the possibility of secondary bleeding after thrombolysis is extremely low; the incidence of spontaneous hemorrhage conversion is 5%
.
7 steps for diagnosis of hemorrhage transformation 1.
Re-examination of imaging at 48 hours after treatment, and re-examination of imaging according to clinical cerebral hemorrhage; 2.
Imaging judgments are judged by independent personnel using blind methods; 3.
Cerebral hemorrhage is described according to anatomical parts; 4.
Distinguish between symptomatic intracerebral hemorrhage (sICH) and asymptomatic intracerebral hemorrhage (aICH); 5.
Determine the clinical symptom deterioration and imaging correlation, divided into: certain, very likely, possible, impossible; 6.
Among them, "definite" And “probably” are reported as sICH, and “probably” or “impossible” are reported as aICH; 7.
Determine the correlation between cerebral hemorrhage and intervention treatment: it occurs within 24 hours after intravenous or arterial thrombolysis; cerebral hemorrhage occurs in Endovascular treatment of brain areas; complications related to angiography
.
Among them, the correlation is also divided into four types: certain, probable, possible, and impossible
.
The impact of bleeding after intravenous thrombolysis on the prognosis (1) Symptomatic hemorrhage transformation (sICH) NINDS: mortality rate is 45%; PH-2: ECASS study shows that the long-term prognosis of patients is unfavorable; PH-1: ECASS study shows Only affect the short-term prognosis; HT-1: ECASSII study showed a good outcome
.
(2) Asymptomatic transformation of bleeding (aICH) NINDS, ECASSII, Atiantis A and B Trials showed no effect on the prognosis of 3 months
.
What are the risk factors for hemorrhage transformation after intravenous thrombolysis? The meta-analysis included 55 intravenous thrombolysis risk factor studies (n=65264) showing that age, high NIHSS score, and high blood sugar were independent risk factors for hemorrhage transformation; the meta-analysis included 14 intravenous thrombolysis risk factor studies of Chinese people (n =2548) showed that: age, atrial fibrillation, history of stroke, history of taking antiplatelet drugs, higher NIHSS score, blood pressure, and blood sugar levels are independent risk factors for hemorrhage transformation after thrombolysis; meta-analysis included 11 studies (n=7194 ) Showed that leukoaraiosis is an independent predictor of sICH; 8 studies (n=2601) included in the meta-analysis showed that more than 10 cerebral microhemorrhage foci may have an impact on hemorrhage transformation (see Figure 3 for a summary)
.
Figure 3 Risk factors for hemorrhage transformation after rt-PA thrombolysis.
Predictive score of hemorrhage transformation after thrombolysis.
Hemorrhage after thrombolysis (HAT) score is a practical, fast and easy-to-operate scoring standard: baseline blood pressure, NIHSS score, CT scan The infarct size can be used for reasonable risk stratification of cerebral hemorrhage after thrombolysis; SEDAN score (0-6 points): baseline blood glucose, CT scan at early admission, age, NIHSS score at admission (≥10 points, score=1), Signs of infarction (yes = 1 point), (high) density cerebral artery signs (yes = 1)
.
The absolute risk of sICH in the derived cohort was scored from 0 to 5, and the corresponding risks were 1.
4%, 2.
9%, 8.
5%, 12.
2%, 21.
7%, and 33.
3%
.
How to prevent cerebral hemorrhage transformation after thrombolysis? Hematology examination: coagulation function, blood routine, platelet count, liver function, kidney function, blood sugar; evaluation of severity of illness: NIHSS score> 25 points or coma; dose not exceeding 0.
9 mg/kg; weighing and accurately calculating the required dose ; Antiplatelet drugs and anticoagulant drugs are not used within 24 hours after thrombolysis
.
Choosing rt-PA as a thrombolytic drug: Relative fibrinolytic specificity: short half-life and fast metabolism; multiple RCTs are widely confirmed, safe and reliable; grasp the treatment time window: 4.
5h (the sooner the better); control blood pressure: SBP>185mmHg , DBP>110mmHg is contraindicated; control hyperglycemia: blood sugar <2.
7mmol/l or>22.
2mmol/l is contraindicated
.
The mechanism of hemorrhage transformation after thrombolysis is related to the structure of rt-PA itself: rt-PA has enzymatic activity, which effectively activates thrombolytic plasminogen as plasmin, and exerts thrombolytic function; rt-PA is retained after thrombolysis The blood-brain barrier (BBB) and its multi-target effects increase the risk of hemorrhage transformation after thrombolysis; reperfusion injury: the incidence of cerebral infarction hemorrhage transformation is significantly positively correlated with the recanalization time; prolonged ischemia time causes a series of complex waterfalls The cascade reaction destroys the BBB, causing harmful components of the blood to penetrate into the brain tissue, forming a vicious circle; BBB permeability increases: animal studies have confirmed that rt-PA can activate PDGF-CC, damage the integrity of BBB, and lead to hemorrhagic transformation
.
The mechanism of hemorrhage transformation after thrombolysis may provide us with corresponding targets for studying the intervention of hemorrhage transformation after thrombolysis, such as: focusing on the mechanism of rt-PA aggravating the destruction of the blood-brain barrier, MMP inhibitors, free radical scavengers, inflammation inhibitors
.
How to choose antithrombotic therapy after thrombolytic bleeding? Chinese and foreign guidelines unanimously recommend anti-platelet therapy with aspirin for most patients in the acute phase; domestic and foreign guidelines recommend dual antiplatelet therapy for high-risk TIA and early ischemic stroke; aspirin is the common recommendation of domestic and foreign guidelines for long-term antithrombotic therapy; domestic Foreign guidelines/consensus recommend that patients with cerebral hemorrhage should resume antithrombotic therapy in time if they have antithrombotic indications, and the timing needs to be individualized; Chinese expert consensus on dual antiplatelet therapy for coronary heart disease (2021): high bleeding risk of receiving dual antibodies Patients should continue to use or resume aspirin treatment.
After gastrointestinal bleeding occurs, it is necessary to decide to continue using the original anti-platelet regimen, or continue taking/resuming aspirin in time based on the risk of rebleeding
.
