从恢复期冠状病毒患者体内采集的静脉免疫球蛋白能否预防新冠？

Treatment with high-dose intravenous immunoglobulin (IVIG) was associated with reduced antibody-induce platelet activation in the serum of three patients who developed a rare blood clotting disorder following vaccination with AstraZeneca’s viral vector Covid-19 vaccine, ChAdOx1 nCoV-19.

大剂量静脉注射免疫球蛋白（IVIG）治疗与三名患者血清中抗体诱导的血小板活化降低有关，这三名患者在接种阿斯利康病毒载体新冠肺炎疫苗ChAdOx1 nCoV-19后出现罕见的凝血障碍。

The report highlighting three early cases of vaccine-induced immune thrombotic thrombocytopenia (VITT) in the weeks following administration of the ChAdOx1 nCoV-19 vaccine in Canada confirmed that treatment with IVIG was associated with increased platelet counts in all three patients.

该报告强调了在加拿大接种ChAdOx1-nCoV-19疫苗后的几周内出现的三例疫苗诱导的免疫性血栓性血小板减少症（VITT）的早期病例，证实了IVIG治疗与所有三名患者的血小板计数增加相关。

In two of the three cases, treatment was associated with an increase in fibrinogen levels and a decrease in D-dimer levels indicative of inhibition of antibody-induced platelet activation and reduced hypercoagulability, wrote researcher Ishac Nazy, PhD, from McMaster University, Ontario, Canada, and colleagues.

Their study was published online June 9 in The New England Journal of Medicine.

来自加拿大安大略省麦克马斯特大学的研究人员Ishac Nazy博士及其同事写道，在这三个病例中，有两个病例的治疗与纤维蛋白原水平升高和D-二聚体水平降低有关，这表明抑制了抗体诱导的血小板活化并降低了高凝状态。

Following early reports of vaccine-induced thrombotic thrombocytopenia associated with the ChAdOx1 nCoV-19 vaccine in mostly younger recipients in Europe, Canadian health officials voted to restrict the vaccine’s roll out to people older than age 54 years. For this reason, the three early VITT cases described in the report were among elderly patients (72-, 63-, and 69-years-old, respectively).

他们的研究于6月9日在线发表在《新英格兰医学杂志》上。

在欧洲大多数年轻的接种者中，早期报告了与ChAdOx1-nCoV-19疫苗相关的疫苗诱导血栓性血小板减少症之后，加拿大卫生官员投票决定将疫苗的推广范围限制在54岁以上的人群。因此，报告中描述的三个早期VITT病例均为老年患者（分别为72岁、63岁和69岁）。

Nazy在接受BreakingMED采访时表示，研究人员首次展示了IVIG如何通过抑制VITT抗体与血小板Fc-γIIa受体的相互作用，有效地减少了VITT患者的血小板活化。

In an interview with BreakingMED, Nazy said the researchers were able to show—for the first time—how IVIG effectively reduced platelet activation in patients with VITT by inhibiting the interaction of VITT antibodies with the platelet Fc-γIIa receptors.

“IVIG works by blocking the clotting antibodies from activating platelets,” he said, adding that the antibodies did not disappear from the patient samples. Instead, the treatment was able to slow down or completely stop platelet activation.

The researchers also showed that the platelet activation test used most often in North America—the serotonin-release assay—can be adapted to detect VITT antibodies by including a reaction well for platelet factor-4 (PF4).

“IVIG通过阻断凝血抗体激活血小板来发挥作用，”他说，并补充说，抗体不会从患者样本中消失。相反，治疗能够减缓或完全停止血小板活化。

研究人员还表明，在北美最常用的血小板活化试验——5-羟色胺释放试验——可以通过包括血小板因子-4（PF4）的反应孔来检测VITT抗体。

他们写道，为了避免血清素释放试验的假阴性结果，观察结果支持在IVIG给药前测试血清中VITT抗体的建议。

病例报告中三名VITT患者中的两名出现肢体动脉血栓，第三名患者出现脑静脉和动脉血栓。

To avoid false negative results on the serotonin-release assay, they wrote, observations support the recommendations to test for VITT antibodies in serum before IVIG administration.

Two of the three VITT patients included in the case report presented with limb-artery thrombosis and the third patient presented with cerebral venous and arterial thrombosis.

72岁患者（患者1）是一名女性，有无明显病史，报告在接种ChAdOx1-nCoV-19疫苗一周后出现左肢疼痛和跛行。她的症状有所进展，在症状出现八天后，她被送进了医院。

这名妇女接受了肝素治疗，并接受了手术取栓。不久后，怀疑VITT，开始使用阿他曲班，血小板计数未见改善。高剂量IVIG与血小板计数在2天内从74000增加到114000每立方毫米有关，有助于口服阿哌沙班出院。

在9天后的随访中，该女性的血小板计数恢复到每立方毫米166000。

The 72-year-old patient (patient 1) was a female with an unremarkable medical history who reported having left limb pain and claudication onset one week after vaccination with the ChAdOx1 nCoV-19. Her symptoms progressed, and she was admitted to a hospital eight days after symptom onset.

The woman was treated with heparin and underwent surgical embolectomy. Soon after, VITT was suspected and argatroban was initiated with no improvement in platelet count seen. High-dose IVIG was associated with a platelet count increase from 74,000 to 114,000 per cubic millimeter during a 2-day period, facilitating discharge with oral apixaban.

At follow-up 9 days later, the woman’s platelet count normalized at 166,000 per cubic millimeter.

患者2是一名63岁的男性，无心血管危险因素或血栓病史，报告接种疫苗后18天开始腿部抽筋。六天后，他到急诊科就诊，CT成像显示左腿出现急性动脉血栓，加上广泛的肺栓塞。该男子接受了低分子量肝素治疗，并接受了手术取栓。

对VITT的怀疑促使从肝素转向磺达肝素和IVIG给药。肝素治疗与初始血小板计数从每立方毫米36000增加到77000有关，随后血小板计数下降。当治疗转换为IVIG时，血小板计数在三天内从27000增加到124000每立方毫升，并在IVIG启动后七天内恢复到640000.

患者3是一名69岁的男性，患有非胰岛素依赖型糖尿病、高血压、阻塞性睡眠呼吸暂停，最近被诊断为前列腺癌（尚未分期）。接种疫苗12天后，他报告头痛和神志不清，并因进行性左侧无力入院。他没有接受肝素治疗，但在VITT确诊后接受了IVIG，随后三天内血小板计数从35000上升到125000。血小板计数下降后，注射了第三剂IVIG，该男子的血小板计数上升至每立方毫米165000。

Patient 2 was a 63-year-old male without cardiovascular risk factors or history of thrombosis who reported leg cramping beginning 18 days after vaccination. He presented to the emergency department six days later and CT imaging showed acute arterial thrombosis in the left leg, plus extensive pulmonary embolism. The man was treated with low-molecular-weight heparin and underwent surgical embolectomy.

Suspicion of VITT prompted a switch from heparin to fondaparinux and IVIG administration. Heparin treatment was associated with an initial platelet count increase from 36,000 to 77,000 per cubic millimeter, followed by a platelet count fall. When the treatment was switched to IVIG, the platelet count rose from 27,000 to 124,000 per cubic milliliter over three days and normalized to 640,000 within seven days of IVIG initiation.

Patient 3 was a 69-year-old man with non-insulin dependent diabetes mellitus, hypertension, obstructive sleep apnea and recently diagnosed prostate cancer (not yet staged). Twelve days after vaccination, he reported having headache and confusion, and was admitted to the hospital with progressive left-sided weakness. He was not treated with heparin but did receive IVIG after VITT was diagnosed and platelet counts rose from 35,000 to 125,000 over the following three days. Following a drop in platelet count, a third dose of IVIG was given, and the man’s platelet count rose to 165,000 per cubic millimeter.

None of the three patients showed clinical evidence of new or progressive thrombosis after IVIG treatment, but all three showed evidence of one or more arterial thrombotic events prior to treatment with IVIG.

三名患者均无IVIG治疗后出现新的或进行性血栓形成的临床证据，但三名患者在IVIG治疗前均出现一次或多次动脉血栓形成事件。

在这三个病例报告之前，大约有40名患者接受了VITT治疗，其中大部分涉及年轻患者。

Among the roughly 40 patients identified with VITT prior to this three-case report, which involved mostly younger patients, arterial thrombosis was reported in five.

“We suspect that older persons with VITT may be more likely to present with arterial thrombotic events,” concluded Nazy and colleagues.

Treatment with high-dose intravenous immunoglobulin was associated with reduced antibody-induce platelet activation in the serum of three patients who developed a rare blood clotting disorder following vaccination with the ChAdOx1 nCoV-19 vaccine.

Following early reports of vaccine-induced thrombotic thrombocytopenia associated with the ChAdOx1 nCoV-19 vaccine in mostly younger recipients in Europe, Canadian health officials voted to restrict the vaccine’s roll out to people older than age 54 years.