Vaccine-induced Immune Thrombotic Thrombocytopenia: Current Evidence, Potential Mechanisms, Clinical Implications, and Future Directions

Abstract Vaccine-induced Immune Thrombotic Thrombocytopenia (VITT) (also termed thrombosis with thrombocytopenia syndrome or vaccine-induced thrombotic thrombocytopenia or vaccine-induced immune thrombocytopenia) is characterized by (i) venous or arterial thrombosis; (ii) mild to severe thrombocytopenia; (iii) positive antiplatelet factor 4 (PF4)–polyanion antibodies or anti-PF4-heparin antibodies detected by the HIT (heparin-induced thrombocytopenia) ELISA assay (iv) occurring 5 to 30 days after ChAdOx1 nCoV-19 (AstraZeneca) or Ad26.COV2.S (Johnson & Johnson/Janssen) vaccination. VITT’s incidence is 1 per 100.000 vaccinated people irrespective of age and up to 1 in 50.000 for people < 50 years of age with the AstraZeneca COVID-19 vaccine. The exact mechanism by which adenovirus-vectored COVID-19 vaccines trigger this syndrome is still unclear, as for the increased risk for acute cerebral sinus venous thrombosis and splanchnic vein thrombosis as compared to other locations of venous thrombotic events. VITT is associated with the detection of anti-PF4 antibodies, unrelated to previous use of heparin therapy. PF4 antibodies are sought to activate platelets via the platelet FcγRIIA receptors leading to further platelet activation that causes thrombosis and thrombocytopenia.

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Heparin-induced thrombocytopenia: when a low platelet count is a mandate for anticoagulation

Hematology ◽

10.1182/asheducation-2009.1.225 ◽

2009 ◽

Vol 2009 (1) ◽

pp. 225-232 ◽

Cited By ~ 14

Author(s):

Thomas L. Ortel

Keyword(s):

Platelet Count ◽

Heparin Therapy ◽

Severe Thrombocytopenia ◽

Drug Induced ◽

Platelet Factor ◽

Heparin Induced Thrombocytopenia ◽

Immune Mediated ◽

Number Of Patients ◽

Increased Risk ◽

Antibody Levels

Abstract Heparin-induced thrombocytopenia (HIT) is an immune-mediated disorder caused by the development of antibodies to platelet factor 4 (PF4) and heparin. The thrombocytopenia is typically moderate, with a median platelet count nadir of ~50 to 60 × 109 platelets/L. Severe thrombocytopenia has been described in patients with HIT, and in these patients antibody levels are high and severe clinical outcomes have been reported (eg, disseminated intravascular coagulation with microvascular thrombosis). The timing of the thrombocytopenia in relation to the initiation of heparin therapy is critically important, with the platelet count beginning to drop within 5 to 10 days of starting heparin. A more rapid drop in the platelet count can occur in patients who have been recently exposed to heparin (within the preceding 3 months), due to preformed anti-heparin/PF4 antibodies. A delayed form of HIT has also been described that develops within days or weeks after the heparin has been discontinued. In contrast to other drug-induced thrombocytopenias, HIT is characterized by an increased risk for thromboembolic complications, primarily venous thromboembolism. Heparin and all heparin-containing products should be discontinued and an alternative, non-heparin anticoagulant initiated. Alternative agents that have been used effectively in patients with HIT include lepirudin, argatroban, bivalirudin, and danaparoid, although the last agent is not available in North America. Fondaparinux has been used in a small number of patients with HIT and generally appears to be safe. Warfarin therapy should not be initiated until the platelet count has recovered and the patient is systemically anticoagulated, and vitamin K should be administered to patients receiving warfarin at the time of diagnosis of HIT.

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A Case of Hereditary Protein S Deficiency Presenting with Cerebral Sinus Venous Thrombosis and Deep Vein Thrombosis at High Altitude

Acta Haematologica ◽

10.1159/000126200 ◽

2008 ◽

Vol 119 (3) ◽

pp. 158-161 ◽

Cited By ~ 13

Author(s):

Velu Nair ◽

A.K. Mohapatro ◽

M. Sreedhar ◽

I.K. Indrajeet ◽

A.K. Tewari ◽

...

Keyword(s):

Deep Vein Thrombosis ◽

Venous Thrombosis ◽

Protein S ◽

Protein S Deficiency ◽

Vein Thrombosis ◽

S Deficiency ◽

Cerebral Sinus Venous Thrombosis ◽

Cerebral Sinus ◽

Deep Vein ◽

Sinus Venous Thrombosis

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Anticoagulation treatment and prophylactic edoxaban for cerebral sinus venous thrombosis in an adolescent with acute lymphoblastic leukemia

SAGE Open Medical Case Reports ◽

10.1177/2050313x211013225 ◽

2021 ◽

Vol 9 ◽

pp. 2050313X2110132

Author(s):

Masaya Koganesawa ◽

Ryosuke Matsuno ◽

Yumiko Sugishita ◽

Ryota Kaneko ◽

Naoko Kawabata ◽

...

Keyword(s):

Young Adults ◽

Acute Lymphoblastic Leukemia ◽

Venous Thrombosis ◽

Induction Therapy ◽

Lymphoblastic Leukemia ◽

Adolescents And Young Adults ◽

Increased Risk ◽

Cerebral Sinus Venous Thrombosis ◽

Cerebral Sinus ◽

Sinus Venous Thrombosis

Pediatric acute lymphoblastic leukemia regimens include large L-asparaginase dosages and steroids, which are associated with an increased risk of venous thromboemboli in adolescents and young adults. Herein, we report the case of an 18-year-old male with acute lymphoblastic leukemia, who was treated with the pediatric regimen, in which edoxaban was employed as a prophylaxis against cerebral sinus venous thrombosis. The event happened on day 20 of induction therapy, when brain magnetic resonance imaging demonstrated a cerebral sinus venous thrombosis in the superior sagittal sinus. Anticoagulation therapy was initiated, and the patient’s symptoms disappeared 3 days later. The induction therapy was restarted after an interruption of 16 days, and the consolidation therapies, which included L-asparaginase and steroids, were completed. Edoxaban was administered as a prophylaxis during the consolidation therapy. There were no further adverse events. Edoxaban could be an effective prophylaxis for coagulation complications in adolescents and young adults with acute lymphoblastic leukemia.

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CEREBRAL SINUS VENOUS THROMBOSIS PADA PENDERITA SYSTEMIC LUPUS ERYTHEMATOSUS

Majalah Kedokteran Neurosains Perhimpunan Dokter Spesialis Saraf Indonesia ◽

10.52386/neurona.v36i3.73 ◽

2020 ◽

Vol 36 (3) ◽

Author(s):

Destika Fahrina ◽

Mohammad Arief Rachman Kemal ◽

Adiel Amaris Syah ◽

Melita Melita ◽

Lyna Soertidewi

Keyword(s):

Systemic Lupus Erythematosus ◽

Venous Thrombosis ◽

Lupus Erythematosus ◽

Low Molecular Weight ◽

Systemic Lupus ◽

Vein Thrombosis ◽

Cerebral Sinus Venous Thrombosis ◽

Cerebral Sinus ◽

Deep Vein ◽

Sinus Venous Thrombosis

CEREBRAL SINUS VENOUS THROMBOSIS IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTABSTRACTCerebral sinus venous thrombosis (CSVT) may sometimes be associated with autoimmune disorder like systemic lupus erythematosus (SLE). It is characterized by dural venous thrombosis which can cause variety of symptoms including headache, convulsion, motor weakness, and decreased level of consciousness. Thrombosis often occurs in the lower extremities in postpartum women due to prolonged bed rest and caesarean section. We reported a 33-year-old woman, who presented with chief complaint of weakness in the left arm and leg, a history of headache and seizures, the following 3 weeks, she had swelling and pain which started at the tip of the left foot then right leg and to the waist. D-dimer level was increased with positive ANA test. Diagnostic investigations include non-contrast head CT scan, CTV, DSA, Doppler ultrasound and thoracoabdominal vasculare CT. Low molecular weight heparin (LMWH) was given for 5 days, continued with oral anticoagulant.Keywords: Cerebral sinus venous thrombosis, deep vein thrombosis, LMWH, postpartum, systemic lupus erythematosusABSTRAKCerebral sinus venous thrombosis (CSVT) dapat berkaitan dengan gangguan autoimun seperti systemic lupus erythematosus (SLE). Hal ini ditandai adanya trombosis vena dural yang menyebabkan berbagai gejala, seperti nyeri kepala, kejang, kelemahan motorik, serta penurunan kesadaran. Trombosis juga sering terjadi di ekstremitas bawah pada perempuan postpartum akibat tirah baring yang lama dan tindakan seksio sesaria. Dilaporkan kasus seorang perempuan 33 tahun dengan keluhan kelemahan tubuh sisi kiri serta riwayat nyeri kepala dan kejang yang 3 minggu kemudian dijumpai bengkak dan nyeri mulai dari ujung kaki kiri kemudian kaki kanan, hingga naik sampai pinggang. Terdapat peningkatan D-dimer dengan tes ANA (+). Pemeriksaan penunjang diagnostik berupa head CT scan nonkontras, CTV, DSA, USG doppler ekstremitas serta CT vascular thoracoabdominal. Pasien diberikan terapi low molecular weight heparin (LMWH) selama 5 hari, dilanjutkan dengan antikoagulan oral.Kata kunci: Cerebral sinus venous thrombosis, deep vein thrombosis, LMWH, postpartum, systemic lupus erythematosus

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Successful treatment of Thrombotic thrombocytopenia with cerebral sinus venous thrombosis following Ad26. COV2 .S vaccination

American Journal of Hematology ◽

10.1002/ajh.26237 ◽

2021 ◽

Author(s):

Gemlyn George ◽

Kenneth D. Friedman ◽

Brian R. Curtis ◽

Stuart E. Lind

Keyword(s):

Venous Thrombosis ◽

Successful Treatment ◽

Cerebral Sinus Venous Thrombosis ◽

Cerebral Sinus ◽

Sinus Venous Thrombosis

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Safety and Efficacy of Argatroban in the Management of Heparin-Induced Thrombocytopenia

Clinical medicine Blood disorders ◽

10.4137/cmbd.s5118 ◽

2011 ◽

Vol 4 ◽

pp. CMBD.S5118 ◽

Cited By ~ 1

Author(s):

Bernd Saugel ◽

Roland M. Schmid ◽

Wolfgang Huber

Keyword(s):

Arterial Thrombosis ◽

Pharmacokinetic Profile ◽

The United States ◽

Heparin Therapy ◽

Direct Thrombin Inhibitor ◽

Thrombin Inhibitor ◽

Heparin Induced Thrombocytopenia ◽

Safety And Efficacy ◽

Increased Risk ◽

Life Threatening

Heparin-induced thrombocytopenia (HIT) is a life-threatening adverse reaction to heparin therapy that is characterized by thrombocytopenia and an increased risk of venous and arterial thrombosis. According to guidelines, in patients with strongly suspected or confirmed HIT all sources of heparin have to be discontinued and an alternative, nonheparin anticoagulant for HIT treatment must immediately be started. For both the prophylaxis of thrombembolic events in HIT and the treatment of HIT with thrombosis the direct thrombin inhibitor argatroban is approved in the United States. The objective of this review is to describe the mechanism of action and the pharmacokinetic profile of argatroban, to characterize argatroban regarding its safety and therapeutic efficacy and to discuss its place in therapy in HIT.

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