SARS-CoV-2 vaccines are not associated with hypercoagulability in apparently healthy people.

Background: SARS-CoV-2 adenoviral vector DNA vaccines have been linked to the rare but serious thrombotic postvaccine complication vaccine-induced immune thrombotic thrombocytopenia. This has raised concerns regarding the possibility of increased thrombotic risk after any SARS-CoV-2 vaccines. Objectives: To investigate whether SARS-CoV-2 vaccines cause coagulation activation leading to a hypercoagulable state. Methods: This observational study included 567 health care personnel; 521 were recruited after the first dose of adenoviral vector ChAdOx1-S (Vaxzevria, AstraZeneca) vaccine and 46 were recruited prospectively before vaccination with a messenger RNA (mRNA) vaccine, either Spikevax (Moderna, n = 38) or Comirnaty (Pfizer-BioNTech, n = 8). In the mRNA group, samples were acquired before and 1 to 2 weeks after vaccination. In addition to the prevaccination samples, 56 unvaccinated blood donors were recruited as controls (total n = 102). Thrombin generation, D-dimer levels, and free tissue factor pathway inhibitor (TFPI) levels were analyzed. Results: No participant experienced thrombosis, vaccine-induced immune thrombotic thrombocytopenia, or thrombocytopenia (platelet count <100 × 109/L) 1 week to 1 month postvaccination. There was no increase in thrombin generation, D-dimer level, or TFPI level in the ChAdOx1-S vaccine group compared with controls or after the mRNA vaccines compared with baseline values. Eleven of 513 (2.1%) participants vaccinated with ChAdOx1-S had anti-PF4/polyanion antibodies without a concomitant increase in thrombin generation. Conclusion: In this study, SARS-CoV-2 vaccines were not associated with thrombosis, thrombocytopenia, increased thrombin generation, D-dimer levels, or TFPI levels compared with baseline or unvaccinated controls. These findings argue against the subclinical activation of coagulation post-COVID-19 vaccination.

Whole blood transfusion and paroxysmal nocturnal haemoglobinuria meet again: Minor incompatibility, major trouble.

BACKGROUND AND OBJECTIVES: The field of transfusion medicine started out with whole blood transfusion to treat severe anaemia and other deficiencies, and then transitioned to component therapy, largely leaving the practice, and experiences, of whole blood transfusions behind. Currently, the field is circling back and whole blood is gaining ground as an alternative to massive transfusion protocols. MATERIALS AND METHODS: Herein we describe a severely anaemic paroxysmal nocturnal haemoglobinuria (PNH) patient initially suspected of suffering from renal haemorrhage, receiving a standard low-titre group O whole blood transfusion during pre-hospital transportation. RESULTS: Following the transfusion, the patient suffered a clinically unmistakable haemolytic transfusion reaction requiring supportive treatment in the intensive care unit. Clinical observations are consistent with an acute haemolytic reaction. The haemolysis was likely due to minor incompatibility between the plasma from the transfused whole blood and the patient's PNH red cells. Recovery was uneventful. CONCLUSION: This revealed an unappreciated contraindication to minor incompatible whole blood transfusion, and prompted a discussion on the distinction between whole blood and erythrocyte concentrates, the different indications for use and the importance of emphasizing these differences. It also calls attention to patient groups where minor incompatibility can be of major importance.

Acute drug-induced immune thrombocytopenia - A work of articaine.

BACKGROUND: Drug-induced immune thrombocytopenia (DITP) is a rare, but serious complication to a wide range of medications. Upon suspicion, one should do a thorough clinical evaluation following proposed diagnostic criteria and seek laboratory confirmation. If confirmed, it is important to ensure avoidance of the drug in the future. STUDY DESIGN AND METHODS: Herein, we describe a young adult male who experienced two bouts of severe thrombocytopenia following dental treatment. The thrombocytopenia was acknowledged due to unexpected hemorrhaging during the procedures. On both occasions, he was exposed to four different drugs, none commonly associated with DITP. After the second episode of severe procedural-related thrombocytopenia, an investigation into the cause was initiated. We describe the clinical approach to elucidate which of the four implicated drugs was responsible for thrombocytopenia and the laboratory work-up done to confirm that the reaction was antibody-mediated and identify the antibody's drug: glycoprotein specificity. An alternative drug was tested both in vivo and in vitro, to identify an option for future procedures. RESULTS: Sequential exposure revealed the local anesthetic substance articaine to induce thrombocytopenia. Laboratory work-up confirmed drug-dependent antibodies (DDAbs) with specificity for the glycoprotein Ib/IX complex, swiftly identified by a bead-based Luminex assay. Further investigations by monoclonal antibody immobilization of platelet antigens assay (MAIPA) revealed a probable GPIb binding site. An alternative local anesthetic, lidocaine, was deemed safe for future procedures. CONCLUSION: Articaine can induce rapid-onset, severe immune-mediated thrombocytopenia causing bleeding complications. A modified bead-based Luminex platelet antigen assay proved a useful addition in the DITP-investigation.

Thrombosis and thrombocytopenia after HPV vaccination.

BACKGROUND: Vaccine-induced immune thrombotic thrombocytopenia (VITT) has so far only been reported after adenovirus vector severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines. OBJECTIVE: We report findings in a 25-year-old woman who presented with thrombocytopenia, venous thrombosis, elevated D-dimer levels, and high levels of platelet-activating antibodies to platelet factor 4-polyanion complexes 10 days after Gardasil 9 vaccination for human papillomavirus (HPV). The patient exhibited clinical and laboratory features in line with the recently defined VITT syndrome, described after adenoviral vector vaccination to prevent coronavirus disease 2019. CONCLUSION: We report a case of VITT following HPV vaccination. This should raise awareness of the possibility of VITT also occurring after other vaccines, not exclusively adenoviral vector-based SARS-CoV-2 vaccines.

An observational study to identify the prevalence of thrombocytopenia and anti-PF4/polyanion antibodies in Norwegian health care workers after COVID-19 vaccination.

BACKGROUND: The COVID-19 vaccine from AstraZeneca (AZD1222) is one of several vaccines introduced to provide immunity against SARS-CoV-2. Recently, more than 50 cases have been reported presenting a combination of thrombosis, thrombocytopenia, and remarkably high levels of anti-platelet factor 4 (PF4)/polyanion antibodies post-AZD1222 vaccination. Now linked to the vaccine, the condition is referred to as vaccine-induced immune thrombotic thrombocytopenia. The European Medicines Agency still recommends vaccination with AZD1222, but several European countries have temporally paused and/or restricted its use because of the perceived risk of this severe side effect. Because there is no description of PF4/polyanion antibody testing in the clinical trials, knowledge about the prevalence of such antibodies in a vaccinated cohort is needed. OBJECTIVES: To investigate prevalence of thrombocytopenia and anti-PF4/polyanion antibodies in a population recently vaccinated with AZD1222. PATIENTS/METHODS: Four hundred and ninety-two health care workers recently vaccinated with the first dose of AZD1222 were recruited from two hospitals in Norway. Study individuals were screened for thrombocytopenia and the presence of anti-PF4/polyanion antibodies with a PF4/PVS immunoassay. Side effects after vaccination were registered. RESULTS: The majority of study participants had normal platelet counts and negative immunoassay. Anti-PF4/polyanion antibodies without platelet activating properties were only detected in six individuals (optical density ≥0.4, range 0.58-1.16), all with normal platelet counts. No subjects had severe thrombocytopenia. CONCLUSIONS: We found low prevalence of both thrombocytopenia and antibodies to PF4/polyanion-complexes among Norwegian health care workers after vaccination with AZD1222.

Thrombocytopenia with acute ischemic stroke and bleeding in a patient newly vaccinated with an adenoviral vector-based COVID-19 vaccine.

We describe the first Danish case of presumed inflammatory and thrombotic response to vaccination with an adenoviral (ChAdOx1) vector-based COVID-19 vaccine (AZD1222). The case describes a 60-year-old woman who was admitted with intractable abdominal pain 7 days after receiving the vaccine. Computed tomography of the abdomen revealed bilateral adrenal hemorrhages. On the following day, she developed a massive right-sided ischemic stroke and magnetic resonance imaging angiography showed occlusion of the right internal carotid artery. The ischemic area was deemed too large to offer reperfusion therapy. During admission, blood tests showed a remarkable drop in platelet counts from 118,000 to 5000 per µl and a substantial increase in D-dimer. The patient died on the sixth day of hospitalization. Blood tests revealed platelet factor 4 reactive antibodies, imitating what is seen in heparin-induced thrombocytopenia. This may be a novel immune-mediated response to the vaccine.