Intracranial hemorrhage, when should hemostatic agents be used? Who can use it?

*Only for medical professionals to read for reference.
From 3 aspects, answer your questions about how to use hemostatic drugs in patients with intracranial hemorrhage.

Intracranial hemorrhage (ICH) has always been the most serious type of stroke, and there is no effective treatment plan.
In patients with intracranial hemorrhage, the probability of hematoma enlargement> 1/3 within 4-6 hours after hemorrhage can be as high as 40%.

For every 10% increase in the volume of a patient’s hematoma, the probability of having a poor prognosis increases by 14%.

The expansion of hematoma volume is currently the only factor that can predict prognosis through biological changes.

Therefore, for patients with intracranial hemorrhage, the use of hemostatic drugs is very important! However, at the 2021 International Stroke Conference, Professor Chitra Venkatasubramanian from the Stanford University Stroke Center (STANFORD STROKE CENTER) pointed out: For patients with intracranial hemorrhage, we are not deciding whether to use hemostatic drugs, but should focus on " Which people need to use (in whom), how to use (How) and when to use (When)" these three aspects, next, let us learn the use of hemostatic drugs together! The use of oral anticoagulants (OAC) for intracranial hemorrhage caused by anticoagulants is becoming more and more widespread, but how to treat OAC-related ICH is still inconclusive.

OAC-related cerebral hemorrhage usually occurs within the treatment range of the normal dose.
If the patient develops cerebral hemorrhage and fails to correct the international normalized ratio (INR) <1.
3 within 4 hours, the risk of hematoma enlargement will increase twice; the mortality rate is as high as 30% -60%; Although intracranial hematomas associated with new oral anticoagulants (DOAC) are uncommon, there is still a 20% mortality rate.

At present, the consensus suggests that the effect of anticoagulant drugs should be reversed as soon as possible to reduce the INR.

However, the timing of anticoagulant reversal and the target value of INR control are still unclear.

At this year's ISC, we may be able to find the answer! Common hemostatic drugs The main hemostatic agent: Tranexamic acid.

Secondary hemostatic agents: ①Reversal-VKA antagonist-vitamin K, prothrombin complex (PCC), fresh frozen plasma (FFP).

②Reversal-DOAC-Idarucizumab, Andexanet alfa.

③Reversal-anti-platelet agents-platelets (Platelets), desmopressin (Desmopressin).

Tranexamic acid, Tranexamic acid Tranexamic acid is an anti-fibrinolytic proteolytic drug.
Previous studies have confirmed that in patients with trauma and postpartum hemorrhage, the use of tranexamic acid can quickly stop bleeding and reduce the death of patients.

The TICH-2 study [Doi:10.
1016/S0140-6736(18)31033-X] published in Lancet in 2018 is an international multi-center, placebo, randomized controlled Phase 3 clinical study that explores "intracranial hemorrhage patients" Whether tranexamic acid treatment in the hyperacute phase can reduce hematoma enlargement and improve patient prognosis", the main clinical outcome: 90-day neurological function (mRS).

The results showed that the trial finally included 2,325 patients with hyperacute intracranial hemorrhage (1161 cases in the tranexamic acid group and 1164 cases in the control group) from 124 hospitals in 12 countries; The mortality rate was lower than that in the placebo group by 101 (9%) vs 123 (11%); OR [0.
73, 0.
53-0.
99, p=0.
0406], but there was no difference in mortality at 90 days 250 (22%) vs 249 ( 21%); Tranexamic acid in patients with hyperacute intracranial hemorrhage, although compared with placebo, tranexamic acid can reduce hematoma enlargement and reduce early mortality and adverse events, but it cannot improve the patient’s 90-day neurological function Defect symptoms.

How to use vitamin K antagonists (VKAs) reversal agents? Regarding the comparison of the anticoagulant effects of FFP and PCC, in The Lancet Neurology, Thorsten Steiner and colleagues reported the results of the first randomized controlled trial (INCH trial) to reverse the anticoagulant effect of patients with intracranial hemorrhage.

Fifty patients with an INR of at least 2 received 20 mL/kg intravenous FFP or 30 IU/kg PCC within 12 hours of the onset of symptoms.

All patients were also injected with 10 mg of vitamin K at the same time.

The main outcome was the reversal of the anticoagulant effect within 3 hours of starting treatment, defined as INR ≤ 1.
2.

Secondary outcomes include hematoma expansion, death, and functional outcomes.

The results showed that: 2 cases (9%) in the FFP group (23 cases), 8 cases (67%) in the PCC group (27 cases), the INR reached ≤1.
2 within 3 hours of treatment [adjusted odds ratio ( OR) 30.
6; 95%CI 4.
7-197.
9; p=0.
0003].

At 90 days, 8 patients (35%) in the FFP group died, while 5 patients (19%) in the PCC group died (p=0.
14).

Unfortunately, this trial was terminated due to uncertainty regarding the safety of rapid INR reversal.

How to use VKAs reversal agent? NCC and the American Society of Critical Care Medicine (SCCM) guidelines (2016) recommend an INR value of 1.
4; When (when to use): when INR>1.
4; Whom (who needs to use): when intracranial hemorrhage is caused by the use of NOAC; How (how to use) What): ①Vitamin 10mg IV (repeated administration according to INR value); ②Preferential use of four-factor prothrombin complex concentrate (4F PCC); ③Repeated use within 15-60min according to INR value; ④If 24h After the INR is still ≥1.
4, FFP can be considered.

How to use the new oral anticoagulant (DOAC) reversal agent? Including Idarucizumab and Andexanet alfa, Idarucizumab is a humanized monoclonal antibody fragment that can quickly, completely and permanently reverse the anticoagulant effect of dabigatran.
It has been approved for use in the United States, Europe and New Zealand.

Andexanet alfa is a recombinant coagulation factor Xa (FXa) inducing molecule developed by Portola Pharmaceuticals, USA, which can quickly and completely reverse the anticoagulant effects of the coagulation factor Xa inhibitors rivaroxaban and apixaban.

How to use DOAC reversal agent? When (when to use): The use of reversal agents is mainly guided by bleeding, and not based on laboratory tests.
If there is bleeding, the reversal drugs can be used directly.

Whom (who needs to use): age <70 years; Glasgow Coma Scale (GCS) ≥ 8 points; bleeding volume <60-70cc, intraventricular hemorrhage (IVH) <5cc (TICH-2); onset time ≤ 2-3h.

How (how to use it): Use Idarucizumab or Andexanet alfa directly.

How to use antiplatelet reversal agents? According to NCC and SCCM guidelines (2016) recommendations: non-surgical intracranial hemorrhage: 1) Desmopressin (DDAVP) 0.
4mcg/kg IV + aspirin or ADP receptor inhibitor.

2) PATCH test: platelet transfusion will worsen bleeding results.

Surgical intracranial hemorrhage: 1) Desmopressin (DDAVP) 0.
4mcg/kg IV+ aspirin or ADP receptor inhibitor.

2) Intravenous infusion of GPIIb/IIIa inhibitors.

Summary: 1.
When and who can use hemostatic drugs? When life-threatening intracranial or intraspinal hemorrhage; when providing preoperative preparation for surgical operation; reasonable clinical signs indicate that the patient has used anticoagulant drugs and accompanied by bleeding symptoms; when combined with clinical, imaging and laboratory examination parameters ( For example, when INR value>1.
4).

2.
Which patients will not benefit from hemostatic drugs? The patient's poor prognosis will not be improved due to hemostasis.

Speaker Chitra Venkatasubramanian, MScSTANFORD STROKE CENTER Source of this article: Medical Neurology Channel This article collation: Saber This article review: Li Tuming Deputy Chief Physician Responsible Editor: Mr.
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