New England: Adjuvant immunoglobulin therapy for COVID-19 vaccine-induced thrombocytopenia

Recently, Covid-19 adenoviral vector vaccine and a rare thrombotic front disorders, the disease is called vaccine-induced immunity thrombotic thrombocytopenia (Vitt)
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Most of the patients diagnosed with VITT are between 20 and 55 years old, and they show unusual thrombosis, such as cerebral venous sinus thrombosis and visceral venous thrombosis

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Thrombosis immune diagnosis

High-dose intravenous immunoglobulin (IVIG) competitively inhibits the interaction of VITT antibody and platelet FcγIIa receptor, thereby reducing platelet activation, this result may be an important treatment consideration
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Because there are few data on the treatment of VITT patients, the recommendation to use IVIG is mainly based on a similar situation to autoimmune HIT treatment, that is, IVIG can rapidly increase platelet counts and reduce hypercoagulability

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High-dose intravenous immunoglobulin (IVIG) competitively inhibits the interaction between VITT antibody and platelet FcγIIa receptor, thereby reducing platelet activation, and large-dose intravenous immunoglobulin (IVIG) competitively inhibits VITT antibody and platelet FcγIIa receptor Body interaction, thereby reducing platelet activation,

Recently, the New England Journal described the response to IVIG treatment of three first patients who were diagnosed with VITT after receiving the ChAdOx1 novel coronavirus vaccine in Canada
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Recently, the New England Journal described the response to IVIG treatment of three first patients who were diagnosed with VITT after receiving the ChAdOx1 novel coronavirus vaccine in Canada
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New England Magazine

After 3 VITT patients received IVIG treatment, serum-induced platelet activation was inhibited

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The age of the patient was 63 to 72 years; one was a female
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Because there are reports that VITT mainly occurs in young people, Canada restricts the use of the ChAdOx1 novel coronavirus -19 vaccine to people 55 years of age or older

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Clinical and laboratory examination data of three VITT patients
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The continuous platelet counts related to anticoagulation therapy and immunoglobulin therapy in 3 patients are shown, as well as the patient's height, weight, and the dose that needs to be considered when administering IVIG

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All three patients tested positive for antibodies against PF4 polyanion complex on ELISA
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Three patients all detected strong positive antibodies against PF4 polyanion complex on ELISA (Table 1)

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Screening

ELISA response before and after IVIG treatment

ELISA response before and after IVIG treatment

Platelet activation test results
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Figure A shows the results of the conventional platelet activation test for heparin-induced thrombocytopenia (serotonin release test) in three study patients

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Platelet activation test results

Heparin and platelet factor 4 (PF4) have different response patterns to serum-induced platelet activation, suggesting that there is heterogeneity in the performance of VITT in serum

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After IVIG treatment was initiated, antibody-induced platelet activation decreased in the serum of all 3 patients
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The findings of this study may reflect that the antibody-induced platelet activation in the body is inhibited and the hypercoagulable state is reduced.
When the patient has severe thrombocytopenia and a variety of unusual thrombi that require therapeutic doses of anticoagulation, increasing the platelet count is particularly important, especially In the case of hemorrhagic transformation after cerebral infarction
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In addition, antibodies related to HIT also activate monocytes and neutrophils through membrane Fcγ receptors
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Because VITT patients may have severe thrombocytopenia lasting for several weeks, early administration of IVIG may be an important adjuvant therapy for VITT anticoagulation therapy
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At present, some VITT treatment guidelines recommend that when VITT is strongly suspected of thrombosis, high-dose IVIG should be administered in advance
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The recommended dose of 1 gram per kilogram of body weight for two consecutive days (ie 2 grams per kilogram total) may be ambiguous because the applicable weight can range from "ideal" to "actual" weight or an intermediate value called "dose" weight

Considering the dose-dependent effect of IVIG in reducing antibody-induced platelet activation, the study recommends using dose weight as much as possible when making these calculations, preferably actual body weight
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Considering the dose-dependent effect of IVIG in reducing antibody-induced platelet activation, the study recommends using dose weight as much as possible when making these calculations, preferably actual body weight

The study also showed that the platelet activation test used in the North American reference laboratory-the serotonin release test-can detect VITT antibodies by including a PF4 response
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Recently, Greinacher et al.
found that supplementation with PF4 (10 μg per milliliter) can help diagnose VITT using a washed platelet activation test based on platelet aggregation
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The serum response patterns of VITT patients obtained in this study are heterogeneous.
They suggest that the detection of HIT and VITT antibodies can be carried out by standard platelet activation test under normal conditions, adding PF4 (≥10 μg per milliliter) without adding heparin It's done
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It is also recommended to measure 0 U per milliliter as a buffer control, because serum-induced serotonin release in the absence of heparin is a feature of autoimmune HIT
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This study supports the recommendation to detect VITT antibodies in serum before IVIG injection to avoid false negative results in the serotonin release test
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In contrast, IVIG treatment failed to inhibit ELISA reactivity
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It is recommended that the detection of HIT and VITT antibodies can be carried out by standard platelet activation test under normal conditions, adding PF4 (≥10 μg per milliliter), and it can be completed without adding heparin.
It is recommended to detect 0 U per milliliter as a buffer control, because in the absence of heparin In this case, serum-induced serotonin release is a feature of autoimmune HIT.
It is recommended to detect VITT antibody in serum before IVIG injection to avoid false negative results of serotonin release test

The study described the first three patients in Canada who were diagnosed with VITT after ChAdOx1 new coronavirus vaccination
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The vaccine received by all three patients was produced by the Serological Institute of India, which supplies about two-thirds of the ChAdOx1 nCoV-19 vaccine in Canada
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Starting from the end of March 2021, VITT cases have been reported in Europe, and the promotion of the AstraZeneca vaccine project in Canada is limited to people over 55 years of age
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This restriction applies to 3 older patients (72, 63 and 69 years old)
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It is worth noting that all three patients had one or more arterial thrombotic events
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In addition, 2 patients had venous thrombosis
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The study speculates that elderly VITT patients may be more prone to arterial thrombotic events
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The study speculates that elderly VITT patients may be more prone to arterial thrombotic events
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The study speculates that elderly VITT patients may be more prone to arterial thrombotic events
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Original source

Bourguignon A, Arnold DM, Warkentin TE, et al.
Adjunct Immune Globulin for Vaccine-Induced Thrombotic Thrombocytopenia [published online ahead of print, 2021 Jun 9].
N Engl J Med.
2021;10.
1056/NEJMoa2107051.
doi:10.
1056/NEJMoa2107051

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Bourguignon A, Arnold DM, Warkentin TE, et al Adjunct Immune Globulin for Vaccine-Induced Thrombotic Thrombocytopenia [published online ahead of print, 2021 Jun 9] N Engl J Med 2021; 10.
1056 / NEJMoa2107051 doi:.
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10.
1056 / NEJMoa2107051 in This message