Spontaneous Heparin-Induced Thrombocytopenia Presenting as Cerebral Venous Sinus Thrombosis

Moores, Ginette; Warkentin, Theodore E.; Farooqi, Mohammed A.; Jevtic, Stefan; Zeller, Michelle P.; Perera, Kanjana

doi:10.1212/cpj.0000000000000805

Cited by 23 publications

(22 citation statements)

References 5 publications

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“…In recent years, it has been recognized that triggers other than heparin can cause a prothrombotic disorder that strongly resembles heparin-induced thrombocytopenia on both clinical and serologic grounds, including certain polyanionic drugs (e.g., pentosan polysulfate, 7 antiangiogenic agent PI-88, 8 and hypersulfated chondroitin sulfate 8 ). Such a prothrombotic syndrome has also been observed in the absence of preceding exposure to any polyanionic medication, such as after both viral and bacterial infections 9 , 10 and knee-replacement surgery. 11 , 12 These various clinical scenarios with apparent nonpharmacologic triggers have been classified under the term autoimmune heparin-induced thrombocytopenia.…”

Section: Discussionmentioning

confidence: 99%

Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination

et al. 2021

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Background Several cases of unusual thrombotic events and thrombocytopenia have developed after vaccination with the recombinant adenoviral vector encoding the spike protein antigen of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (ChAdOx1 nCov-19, AstraZeneca). More data were needed on the pathogenesis of this unusual clotting disorder. Methods We assessed the clinical and laboratory features of 11 patients in Germany and Austria in whom thrombosis or thrombocytopenia had developed after vaccination with ChAdOx1 nCov-19. We used a standard enzyme-linked immunosorbent assay to detect platelet factor 4 (PF4)–heparin antibodies and a modified (PF4-enhanced) platelet-activation test to detect platelet-activating antibodies under various reaction conditions. Included in this testing were samples from patients who had blood samples referred for investigation of vaccine-associated thrombotic events, with 28 testing positive on a screening PF4–heparin immunoassay. Results Of the 11 original patients, 9 were women, with a median age of 36 years (range, 22 to 49). Beginning 5 to 16 days after vaccination, the patients presented with one or more thrombotic events, with the exception of 1 patient, who presented with fatal intracranial hemorrhage. Of the patients with one or more thrombotic events, 9 had cerebral venous thrombosis, 3 had splanchnic-vein thrombosis, 3 had pulmonary embolism, and 4 had other thromboses; of these patients, 6 died. Five patients had disseminated intravascular coagulation. None of the patients had received heparin before symptom onset. All 28 patients who tested positive for antibodies against PF4–heparin tested positive on the platelet-activation assay in the presence of PF4 independent of heparin. Platelet activation was inhibited by high levels of heparin, Fc receptor–blocking monoclonal antibody, and immune globulin (10 mg per milliliter). Additional studies with PF4 or PF4–heparin affinity purified antibodies in 2 patients confirmed PF4-dependent platelet activation. Conclusions Vaccination with ChAdOx1 nCov-19 can result in the rare development of immune thrombotic thrombocytopenia mediated by platelet-activating antibodies against PF4, which clinically mimics autoimmune heparin-induced thrombocytopenia. (Funded by the German Research Foundation.)

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Section: Discussionmentioning

confidence: 99%

Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination

et al. 2021

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“…Patients frequently experience moderate-to-severe thrombocytopenia manifesting as venous or arterial thrombi (sometimes both simultaneously). Rarely, a syndrome resembling HIT on both clinical and laboratory grounds-"spontaneous HIT syndrome"-occurs following infection in the absence of heparin therapy [53], but this has not been reported in COVID-19.…”

Section: Heparin-induced Thrombocytopenia (Hit)mentioning

confidence: 99%

The unique characteristics of COVID-19 coagulopathy

et al. 2020

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Thrombotic complications and coagulopathy frequently occur in COVID-19. However, the characteristics of COVID-19-associated coagulopathy (CAC) are distinct from those seen with bacterial sepsis-induced coagulopathy (SIC) and disseminated intravascular coagulation (DIC), with CAC usually showing increased D-dimer and fibrinogen levels but initially minimal abnormalities in prothrombin time and platelet count. Venous thromboembolism and arterial thrombosis are more frequent in CAC compared to SIC/DIC. Clinical and laboratory features of CAC overlap somewhat with a hemophagocytic syndrome, antiphospholipid syndrome, and thrombotic microangiopathy. We summarize the key characteristics of representative coagulopathies, discussing similarities and differences so as to define the unique character of CAC.

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“…The response suggests a disease mechanism similar to spontaneous heparininduced thrombocytopenia (HIT), a form of autoimmune HIT, which has been previously reported to cause CVST, as well as other forms of thrombosis. [6][7][8][9] Among patients diagnosed with deep vein thrombosis and pulmonary embolism prior to the COVID-19 pandemic, the estimated proportion with thrombocytopenia was 14%. 10 The frequency of thrombocytopenia, HIT, and PF4/heparin antibodies in CVST prior to the COVID-19 pandemic are unknown.…”

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confidence: 99%

Frequency of Thrombocytopenia and Platelet Factor 4/Heparin Antibodies in Patients With Cerebral Venous Sinus Thrombosis Prior to the COVID-19 Pandemic

Kammen

Heldner

Brodard

et al. 2021

JAMA

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IMPORTANCE Cases of cerebral venous sinus thrombosis in combination with thrombocytopenia have recently been reported within 4 to 28 days of vaccination with the ChAdOx1 nCov-19 (AstraZeneca/Oxford) and Ad.26.COV2.S (Janssen/Johnson & Johnson) COVID-19 vaccines. An immune-mediated response associated with platelet factor 4/heparin antibodies has been proposed as the underlying pathomechanism.OBJECTIVE To determine the frequencies of admission thrombocytopenia, heparin-induced thrombocytopenia, and presence of platelet factor 4/heparin antibodies in patients diagnosed with cerebral venous sinus thrombosis prior to the COVID-19 pandemic. DESIGN, SETTING, AND PARTICIPANTSThis was a descriptive analysis of a retrospective sample of consecutive patients diagnosed with cerebral venous sinus thrombosis between January 1987 and March 2018 from 7 hospitals participating in the International Cerebral Venous Sinus Thrombosis Consortium from Finland,

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Spontaneous Heparin-Induced Thrombocytopenia Presenting as Cerebral Venous Sinus Thrombosis

Abstract: Spontaneous HIT syndrome should be considered in any patient presenting with unexplained thrombocytopenia and unprovoked arterial and/or venous thrombosis, including CVST.

Cited by 23 publications

References 5 publications

Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination

Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination

The unique characteristics of COVID-19 coagulopathy

Frequency of Thrombocytopenia and Platelet Factor 4/Heparin Antibodies in Patients With Cerebral Venous Sinus Thrombosis Prior to the COVID-19 Pandemic

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