Thromboprophylaxis in gynaecology: a review of current evidence

Key content: Thromboembolism is a major cause of preventable morbidity and mortality. Hospital acquired thrombosis (HAT) accounts for 50-60% of all thromboembolic events. As well as effects on patient safety, there are considerable cost implications to both prophylaxis and treatment. While guidance exists on thromboprophylaxis for patients in obstetrics and those undergoing general surgery, there is a paucity of guidance relating to gynaecological practice. Increasing prevalence of risk factors and multimorbidity is paralleled by higher risk of thromboembolic events. Gynaecological surgery presents some unique risk factors for thrombosis. Learning objectives: To understand the basic pathophysiology of thrombosis in relation to risk factors particularly relevant to gynaecology and pelvic surgery. To know the current evidence in key areas relevant to gynaecological practice: early pregnancy;day case surgery;minimally invasive gynaecological surgery;open and complex benign gynaecology and gynaecological oncology. To be aware of proposed guidance on risk assessment and prophylaxis in thrombosis as relevant to the gynaecologist based on current evidence. Ethical issues: Problems with thromboprophylaxis in high-risk patients include noncompliance and refusing animal products/injections. Clinicians may be reluctant to institute thromboprophylaxis, most times because of the possible risks of bleeding. Copyright © 2022 Royal College of Obstetricians and Gynaecologists.

Optimal anticoagulation intensity for patients with COVID-19 treated with Tocilizumab

Background: Tocilizumab reduces the need and the duration of organ support and provides a survival benefit for patients at the early stages of COVID-19 (Coronavirus Disease 2019) that have increasing oxygen needs and a significant inflammatory response. Contrary to expectations that this treatment would, also, break the vicious cycle of immunothrombosis of COVID-19, it has been debated whether it is associated with a conversely increased venous thromboembolism (VTE) incidence. In the interim, society guidelines have updated their recommendations advising a prophylactic over that of an intermediate or treatment dose of anticoagulation but there is a lack of evidence based for this group of patients. Aim(s): The purpose of this study was to compare the incidence of VTEs in patients with COVID-19 treated with Tocilizumab in relationship to the thromboprophylaxis dose determined by NICE guidelines. Method(s): A retrospective, cohort study was performed including all patients with COVID-19 admitted at NHS Hillingdon Hospital (UK) who required Tocilizumab between December 2020 and September 2021. Result(s): Sixty-three patients (20 females;43 males) with a median age of 63 y.o. (17-83) were analysed (Table 1). A Spearman's rank correlation was run to determine the relationship between the anticoagulation strategy and the thromboembolic risk in this context. A moderate negative correlation was found between the anticoagulation intensity and the risk of a VTE, r (61) = -0.470, p = 0.000. Binary logistic regression was then used to determine the relationship between anticoagulation intensity and VTEs and Multinomial Logistic Regression for the opposite relationship. Treatment dose thromboprophylaxis is related with more VTEs however this is likely a reflection that patients with VTEs receive appropriate antithrombotic therapy (Table 2). Conclusion(s): The present study suggests that patients with COVID-19 that receive Tocilizumab are not at increased thromboembolic risk and thus standard thromboprophylaxis should suffice. Findings should be confirmed in randomized controlled trials. (Table Presented).

Sars-cov-2 vaccination in patients with pre-existing immune thrombocytopenia

Introduction: Cases of de novo immune thrombocytopenia (ITP), including a fatality following SARS-CoV-2 vaccination in a previously healthy recipient, led to studying its impact in pre-existing ITP. Published reports are limited but suggest that most patients with ITP tolerate the COVID-19 vaccines well without frequent ITP exacerbations (Kuter, BJH, 2021). Data regarding risk factors for exacerbation and relationship of response to first dose to that of second dose are limited. Methods: Data for patients with pre-existing ITP were obtained via 3 sources. First, via a ten-center retrospective study of adults with ITP who received a SARS-CoV-2 vaccine between December 2020 and March 2021 and had a post-vaccination platelet count (n=117);9 centers were in the United States. Eighty-nine percent of patients received mRNA-based vaccines. The second and third sources of data were surveys distributed by the Platelet Disorder Support Association (PDSA) and the United Kingdom ITP Support Association. A 'stable platelet count' was defined as a post-vaccination platelet count within 20% of the pre-vaccination level. ITP exacerbation was defined as any one or more of: platelet decrease ≥ 50% compared to pre-vaccination baseline, platelet decrease by >20% compared to prevaccination baseline with platelet nadir < 30x10 9/L, receipt of rescue therapy for ITP. Continuous variables were described as mean ±SD or median [interquartile range];categorical variables were described as n (%). Relative risks and 95% confidence interval were calculated to estimate strength of association. Results: Among 117 patients with pre-existing ITP from 10 centers who received a SARS-CoV-2 vaccine, mean age was 63±17 years, 62% were female, with median 12 [4-23] years since diagnosis of ITP;patients had received a median of 3 [2-4] prior medical treatments. Sixtynine patients were on ITP treatment at the time of vaccination (Table 1). There was an almost even distribution of platelet count response following each vaccine dose. In 109 patients with data for dose 1, platelet counts increased in 32 (29%), were stable in 43 (39%), and decreased in 34 (31%);in 70 patients following dose 2, platelet counts increased in 24 (34%), were stable in 25 (36%), and decreased in 21 (30%) (Figure 1). Nineteen (17%) patients experienced an ITP exacerbation following the first dose and 14 (20%) of 70 after a second dose. In total, fifteen patients received and responded to rescue treatments (n = 6 after dose 1, n = 8 after dose 2, n = 1 after both doses). Of 7 patients who received rescue treatment after dose 1, 5 received dose 2 and only 1/5 received rescue treatment again. Rescue consisted of increased dose of ongoing medication, steroids, IVIG, and rituximab. Splenectomized persons and those who received 5 or more prior lines of medical therapy were at highest risk of ITP exacerbation. Only 1 of 47 patients who had neither undergone splenectomy nor received 5 or more lines of therapy developed ITP exacerbation after dose 1. There were 14 patients offtreatment at the time of dose 1 and 7 patients at time of dose 2;1 patient in each group developed ITP exacerbation with both these having had normal counts prior to vaccination and having undergone splenectomy. In 43 patients whose platelet counts were stable or increased after dose 1 and received dose 2, only 6 (14%) had platelet decreases to <50 x10 9/L after dose 2. Age, gender, vaccine type, and concurrent autoimmune disease did not impact post-vaccine platelet counts. In surveys of 57 PDSA and 43 U.K. ITP patients, similar rates of platelet change were seen (33% of participants reported decreased platelet count in both surveys) and prior splenectomy was significantly associated with worsened thrombocytopenia in each. Conclusions: Thrombocytopenia may worsen in pre-existing ITP post-SARS-CoV2-vaccination but when ITP exacerbation occurred, it responded well to rescue treatment. No serious bleeding events were noted. Rescue treatment was needed in 13% of patients. Proactive vaccination surveillance of patien s with known ITP, especially those post-splenectomy and with more refractory disease, is indicated. These findings should encourage patients with ITP to not only be vaccinated, but to receive the second dose when applicable to ensure optimal immunization. Rituximab interferes with vaccination response and ideally would be held until a minimum of 2 weeks after completion of vaccination.

D-Dimer and Thrombosis in COVID-19

The coronavirus disease 2019 (COVID-19) pandemic has taken medical community by surprise, but it also saw significant advances in understanding of infection induced coagulopathy. Pulmonary and macrovascular thrombosis is one of the hallmarks of this pandemic and has intrigued vascular surgeons world over. In this review, the lessons learnt from COVID-19 coagulopathy are summarised with some perspectives on role of newer concepts of immune mediated thrombosis and endothelial inflammation. D-dimers have become one of the most discussed inflammatory marker and also one of the commonest blood tests ordered in the COVID-19 pandemic. Its usefulness in management of COVID induced thrombosis has been a matter of debate and this article looks in to evidence based application of D-dimer in clinical practice. Role of Heparins, Direct Oral Anticoagulants (DOACs) and anti-platelets in prophylaxis and management of vascular thrombosis has also been summarised.

Isth registry on pregnancy and COVID-19 associated coagulopathy (COVPREG-COAG)-first report

Background: Increased susceptibility to severe illnesses has been reported in pregnancy, following infection with SARS-CoV-2 resulting in COVID-19, in part evoked by pregnancy-related physiologic and immunologic changes. In the non-pregnant population, COVID-19 associated coagulopathy (CAC) with a thrombotic phenotype has been described in those with severe illness. Pregnancy is an inherently prothrombotic state, yet data on CAC in pregnancy remains scarce. The ISTH SSC for Women's Health Issues in Thrombosis and Haemostasis developed the international registry (COV-PREG-COAG) addressing CAC in pregnancy. Aims: To examine the occurrence of CAC during pregnancy, its characteristics, association with disease severity, and effects on maternal and fetal outcomes. Methods: Physicians worldwide were invited to participate. The ISTH REDCap online platform, which utilizes robust data confidentiality and security protocols for data capture, was adopted. Data included: pregnancy demographics, disease state, comorbidities, haemostatic parameters, details of coagulopathy and its treatment, as well as fetal and maternal outcomes. As of March 8, 2021, 340 COVID-19 affected pregnancies were reported to COV-PREG-COAG. Results: Table 1 summarizes relevant findings. Over 80% of COVID-19 occurred in the third trimester and 55% of women were asymptomatic. Most common symptoms included cough (47%), fever (39%), shortness of breath (25%) and anosmia (17%). Comorbid pathologies were reported as follows: obesity (66%), respiratory illnesses (7.6%) and diabetes (2.4%). Among 336 women with complete information, 5% were hospitalized, 3.3% had severe disease, and 1.3% required ICU admission. Two patients with CAC required ECMO/mechanical ventilation. CAC features included: prolonged PT/APTT (9.1%), thrombocytopenia (4.9%), elevated D-dimer (4.6%), hyper-fibrinogenemia (5%). Non of the patients developed hypofibrinogenemia. Sixty-six percent of women received postpartum thromboprophylaxis. There was one venous thromboembolic event and no maternal deaths. Conclusions: This early report from the ISTH registry demonstrates that CAC and thrombotic events are infrequent in COVID-19 affected pregnancies. Further data is required before drawing definite conclusions.

Biomarkers for the prediction of venous thromboembolism in critically ill COVID-19 patients.

BACKGROUND: Venous thromboembolism (VTE) is a frequent complication in critically ill patients with coronavirus disease 2019 (COVID-19) and is associated with mortality. Early diagnosis and treatment of VTE is warranted. OBJECTIVE: To develop a prediction model for VTE in critically ill COVID-19 patients. PATIENTS AND METHODS: In this retrospective cohort study, 127 adult patients with confirmed COVID-19 infection admitted to the intensive care unit of two teaching hospitals were included. VTE was diagnosed with either ultrasound or computed tomography scan. Univariate receiver operating characteristic (ROC) curves were constructed for Positive End Expiratory Pressure, PaO2/FiO2 ratio, platelet count, international normalized ratio, activated partial thromboplastin time as well as levels of fibrinogen, antithrombin, D-dimer and C-reactive protein (CRP). Multivariate analysis was done using binary linear regression. RESULTS: Variables associated with VTE in both univariate and multivariate analysis were D-dimer and CRP with an area under the curve (AUC) of 0.64, P = 0.023 and 0.75, P = 0.045, respectively. Variables indicating hypoxemia were not predictive. The ROC curve of D-dimer and CRP combined had an AUC of 0.83, P < 0.05. Categorized values of D-dimer and CRP were used to compute a mean absolute risk for the combination of these variables with a high positive predictive value. The predicted probability of VTE with a D-dimer > 15 in combination with a CRP > 280 was 98%. The negative predictive value of D-dimer was low. CONCLUSION: Elevated CRP and D-dimer have a high positive predictive value for VTE in critically ill COVID-19 patients. We developed a prediction table with these biomarkers that can aid clinicians in the timing of imaging in patients with suspected VTE.

Understanding the COVID-19 coagulopathy spectrum

The SARS-Cov-2 (COVID-19) pandemic has already claimed over 200,000 lives. Quite early on in this pandemic, it was recognised that the virus triggers the immune system leading to a cytokine storm in some severely ill patients [1]. This hyper-responsiveness has been suggested to be the predominant aetiology for clinical deterioration and mortality in patients with this infection [2]. More recently, there have been several reports of increased thrombotic events in these patients [3-6]. From a laboratory perspective, this hypercoagulability is reflected in the marked elevation of the fibrinolytic marker, D-dimer, in almost all hospitalised COVID-19 patients [7]. We must, therefore, ask ourselves what is the link between the extremes of the immune system, presenting as cytokine storm, and the extremes of coagulation, presenting as arterial and venous thromboembolism?