Introduction Timely diagnosis and treatment of portal vein thrombosis (PVT) is crucial to prevent morbidity and mortality. However, current imaging tests cannot always accurately differentiate acute from chronic (nonocclusive) PVT. Magnetic resonance noncontrast thrombus imaging (MR-NCTI) has been shown to accurately differentiate acute from chronic venous thrombosis at other locations and may also be of value in the diagnostic management of PVT. This study describes the first phase of the Rhea study (NTR 7061). Our aim was to select and optimize MR-NCTI sequences that would be accurate for differentiation of acute from chronic PVT. Study Design The literature was searched for different MRI sequences for portal vein and acute thrombosis imaging. The most promising sequences were tested in a healthy volunteer followed by one patient with acute PVT and two patients with chronic PVT, all diagnosed on (repetitive) contrast-enhanced computed tomography (CT) venography to optimize the MR-NCTI sequences. All images were evaluated by an expert panel. Results Several MR-NCTI sequences were identified and tested. Differentiation of acute from chronic PVT was achieved with 3D T1 TFE (three-dimensional T1 turbo field echo) and 3D T1 Dixon FFE (three-dimensional T1 fast field echo) sequences with best image quality. The expert panel was able to confirm the diagnosis of acute PVT on the combined two MR-NCTI sequences and to exclude acute PVT in the two patients with chronic PVT. Conclusion Using 3D T1 TFE and 3D T1 Dixon FFE sequences, we were able to distinguish acute from chronic PVT. This clinical relevant finding will be elucidated in clinical studies to establish their test performance.
Background and Aims: Since the introduction of SARS-CoV-2 vaccines, several cases of vaccine-induced immune thrombocytopenia and thrombosis (VITT) have been described, especially cerebral vein thrombosis. We aimed to retrospectively collect all new cases of acute onset first or recurrent splanchnic vein thrombosis (SVT) following a recent SARS-CoV-2 vaccination within the Vascular Liver Disease Group network. Approach and Results: New cases of SVT were identified from April 2021 to April 2022; follow-up was completed on December 31, 2022. Criteria to define VITT were derived from previous studies. Data from a pre-COVID cohort of patients with SVT (N=436) were used for comparison of clinical presentation, etiology, and outcome. Twenty-nine patients were identified with SVT occurring with a median of 11 days (range 2–76) after the first (48%), second (41%), or third (10%) vaccination (ChAdOx1 nCov-19 (n=12) or BNT162b2 (n=14), other (n=3) Only 2 patients(7%) fulfilled criteria for definite VITT. Twenty (69%) had SVT at multiple sites, including 4 (14%) with concomitant extra-abdominal thrombosis. Only 28% had an underlying prothrombotic condition, compared to 52% in the pre-COVID SVT cohort ( p =0.01). Five patients (17%) underwent bowel resection for mesenteric ischemia, compared with 3% in pre-COVID SVT ( p <0.001). Two patients died shortly after diagnosis (7%). Conclusions: Although definite VITT was rare, in 72% of cases, no other cause for SVT could be identified following SARS-CoV-2 vaccination. These cases were different from patients with nonvaccine–related SVT, with lower incidence of prothrombotic conditions, higher rates of bowel ischemia, and poorer outcome. Although SVT after SARS-CoV-2 vaccination is rare in absolute terms, these data remain relevant considering ongoing revaccination programs.
Coronavirus disease 19 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can be associated with changes in platelet count [1, 2]. Thrombocytopenia has been reported in up to 40% of COVID-19 infections [3-5] and is an important marker for morbidity and mortality [1, 2, 5]. Hence, monitoring of platelet counts is important in diagnosis and treatment of COVID-19 patients. Thrombocytopenia can be a result of the COVID-19 infection itself (septicaemia), diffuse intravascular coagulation (DIC), medication or a COVID-19-associated immune thrombocytopenic purpura (ITP) [6]. A rare and often missed alternative explanation of thrombocytopenia is pseudothrombocytopenia [7]. Pseudothrombocytopenia or spurious thrombocytopenia is an in vitro phenomenon of platelet agglutination caused by an anticoagulant, usually ethylenediaminetetraacetic acid (EDTA), resulting in a falsely lowered automated platelet count [8]. The mechanism of pseudothrombocytopenia is not clearly defined, but it is suggested to be an immunologically mediated phenomenon of platelet clumping due to the formation of immune complexes between naturally occurring autoantibodies and cryptic epitopes of the glycoprotein IIb/IIIa complex on the platelet membrane that are exposed by the EDTA anticoagulant used for routine blood sample collections [9]. This phenomenon has been previously reported to be associated with autoimmune diseases and infections [10], such as hepatitis A [11], mononucleosis [12] and Plasmodium falciparum malaria [13]. It has a reported incidence between 0.03% and 0.27% among the general population [14]. Here, we report the first patient with pseudothrombocytopenia related to COVID-19 infection and its natural course. Our patient is a 54-year-old woman with a history of sarcoidosis diagnosed in October 2019, for which she was still being treated with daily prednisolone 7.5 mg (December 2019) and weekly methotrexate 12.5 mg (January 2020). She previously had a stable normocytic anaemia and normal platelet counts. Approximately 10 days after onset of respiratory symptoms, she presented with progressive respiratory failure (and a need for high-flow oxygen therapy) secondary to COVID-19 bilateral pneumonia with a positive SARS-CoV-2 polymerase chain reaction (PCR) test on day of presentation in our hospital. After a chest CT-angiography scan excluded pulmonary embolism, empirical treatment according to local protocol with dexamethasone (prednisolone was discontinued on admission), ceftriaxone, ciprofloxacin and prophylactic low-molecular weight heparin (nadroparin) was started. A full blood count on the day of presentation showed a stable haemoglobin level of 9.9 g/dl, with normal leukocyte (7.0 × 109/L) and platelet (236 × 109/L) counts. The following day, a marked fall in platelet count to 54 × 109/L was noted (measured with the Coulter impedance method on EDTA)—a trend that continued the following days to a nadir platelet count of 6 × 109/L on day 10 after presentation (Figure 1). On this day, dexamethasone and methotrexate were discontinued; the latter because a possible causal relationship with the thrombocytopenia was postulated. Further laboratory work showed a slightly elevated lactate dehydrogenase (427 U/L), normal haptoglobin, normal prothrombin (PT) and activated partial thromboplastin time (aPTT) and elevated D-dimers (3.50 mg/L), excluding a thrombotic microangiopathy. No further testing for diffuse intravascular coagulation (DIC) or heparin-induced thrombocytopenia (HIT) was performed at this time. HIV-serology test was negative. There were no clinical signs of bleeding or thrombosis. On day 10 after presentation, platelet count in a citrate blood sample was 129 × 109/L. Analysis of a peripheral blood film at the same moment showed platelet agglutination in EDTA as well as in citrate, although much less evident (Figure 2). Hence, the diagnosis of pseudothrombocytopenia was confirmed, which also marked the misdiagnosis of a true thrombocytopenia at first in this patient. In the following weeks, together with SARS-CoV-2 seroconversion and clinical recovery, we noted a positive trend in platelet counts (Figure 1): EDTA 28 × 109/L and citrate 217 × 109/L in week 6 after nadir, EDTA 99 × 109/L and citrate 249 × 109/L in week 8 after nadir. The phenomenon seems transient, as it was reported to be in the only other publication describing a similar case, although platelet transfusion was given in this case [7]. SARS-CoV-2 IgM and total antibodies were first measured, using the Wantai ELISA-test (WS-1196 and WS-1096), in week 7 after diagnosis of COVID-19 infection, already showing sufficient SARS-CoV-2 seroconversion. In COVID-19-related pseudothrombocytopenia, we suggest a possible link with SARS-CoV-2 IgM antibodies and hypothesize an EDTA-dependent immune-complex formation with cryptic platelet membrane epitopes. To test this, we incubated patient serum with EDTA-blood of a universal donor, but this did not induce platelet agglutination. Taken together, this may suggest that generation of cryptic epitopes is patient specific. In conclusion, we illustrate the importance of considering pseudothrombocytopenia in COVID-19-associated thrombocytopenia. This is the first case of COVID-19-associated pseudothrombocytopenia in which we also describe the transience of this diagnosis. It is essential to recognize this in vitro phenomenon, as this falsely lowered automated platelet count is not associated with a clinical bleeding tendency, does not have any therapeutic consequences (platelet transfusion nor discontinuation of essential medication) and is self-limiting, as shown in our patient. In the differential diagnosis of COVID-19-associated thrombocytopenia, exclusion of pseudothrombocytopenia is therefore critical. The authors declare that there is no conflict of interest. R. Van Dijck, M.N. Lauw and A.J.G. Jansen conceived the idea. R. Van Dijck wrote the manuscript. R. Van Dijck and H. Russcher provided Figures 1 and 2. A.J.G. Jansen, M.N. Lauw, M. Swinkels and H. Russcher reviewed and critically evaluated the manuscript. All authors approved the final version of the manuscript.
Thrombosis is a frequent and severe complication in patients with coronavirus disease 2019 (COVID-19) admitted to the intensive care unit (ICU). Lupus anticoagulant (LA) is a strong acquired risk factor for thrombosis in various diseases and is frequently observed in patients with COVID-19. Whether LA is associated with thrombosis in patients with severe COVID-19 is currently unclear.To investigate if LA is associated with thrombosis in critically ill patients with COVID-19.The presence of LA and other antiphospholipid antibodies was assessed in patients with COVID-19 admitted to the ICU. LA was determined with dilute Russell's viper venom time (dRVVT) and LA-sensitive activated partial thromboplastin time (aPTT) reagents.Of 169 patients with COVID-19, 116 (69%) tested positive for at least one antiphospholipid antibody upon admission to the ICU. Forty (24%) patients tested positive for LA; of whom 29 (17%) tested positive with a dRVVT, 19 (11%) tested positive with an LA-sensitive aPTT, and 8 (5%) tested positive on both tests. Fifty-eight (34%) patients developed thrombosis after ICU admission. The odds ratio (OR) for thrombosis in patients with LA based on a dRVVT was 2.5 (95% confidence interval [CI], 1.1-5.7), which increased to 4.5 (95% CI, 1.4-14.3) in patients at or below the median age in this study (64 years). LA positivity based on a dRVVT or LA-sensitive aPTT was only associated with thrombosis in patients aged less than 65 years (OR, 3.8; 95% CI, 1.3-11.4) and disappeared after adjustment for C-reactive protein.Lupus anticoagulant on admission is strongly associated with thrombosis in critically ill patients with COVID-19, especially in patients aged less than 65 years.
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: Primary objectives of this review are: to investigate and summarize whether thromboprophylactic measures are effective in reducing the incidence of VTE during asparaginase therapy in primary ALL remission induction treatment for pediatric and adult patients; to investigate the impact of thromboprophylaxis used during primary ALL remission induction treatment on overall survival. Secondary objectives of this review are: to investigate and summarize the adverse effects of thromboprophylactic measures during asparaginase therapy in primary ALL remission induction treatment, to address their safety (Loke 2011); to investigate and summarize which thromboprophylactic measure is the most effective in reducing the VTE incidence during asparaginase therapy in primary ALL remission induction treatment; to investigate the impact of thromboprophylaxis used during asparaginase therapy in primary ALL remission induction treatment on ALL treatment outcome, expressed in complete remission rates.
