Should treatment for blood clots be routine in some Covid patients?

My heading above is a plain English version of the first academic heading below. Blood clots can do a lot of harm so are a serious problem. But they can be treated with considerable success by blood thinners such as Warfarin. But Warfarin has its problems too. It can cause bleeding. So, obviously, you use it only when it is clearly needed.

And the BIG question is whether you should use it for prevention. Should you give it to a patient BEFORE they get any symptoms?

Nobody is saying that you should give thinners to ALL Covid patients so the question is whether you should give it to high-risk patients? If so, how do you identify the patients most likely to suffer from blood clots?

So you can see that there is a real problem there. The study from Oxford University below tries to solve that puzzle

And there are some categories of patient who usually ARE high risk. We can identifty some patients as being at risk. So how great does the risk have to be before you give a patient thinners? The article below tries to answer that and concludes that there are some cases that should get preventive treatment.

But the problem is a difficult one so I reproduce below the Abstract from the original Oxford article plus two further comments on it.

A crude summary of the findings is that fat old guys should be given thinners. I am old and a bit overweight so if ever I get Covid, I should probably be given a low dose of thinners

Clinical and Genetic Risk Factors for Acute Incident Venous Thromboembolism in Ambulatory Patients With COVID-19

JunQing Xie et al.

Key Points

Question What is the 30-day acute risk of venous thromboembolism (VTE) among ambulatory patients with COVID-19, and what are the clinical and genetic risk factors predisposing them to developing post–COVID-19 VTE?

Findings In this retrospective cohort study of 18 818 outpatients with COVID-19 and 93 179 propensity score–matched noninfected participants, a higher VTE incidence was observed in the former (hazard ratio, 21.42); however, this risk was considerably attenuated among the fully vaccinated, after breakthrough infection. Older age, male sex, obesity, no vaccination or partial vaccination, and inherited thrombophilia were independent risk factors for COVID-19–associated VTE.

Meaning The results of this study suggest that ambulatory patients with COVID-19, either vaccinated or not, present a clinically relevant increased risk of incident VTE during the acute phase, with the risk pronounced by factors of older age, male sex, obesity, incomplete vaccination, and factor V Leiden thrombophilia.


Importance The risk of venous thromboembolism (VTE) in ambulatory COVID-19 is controversial. In addition, the association of vaccination with COVID-19–related VTE and relevant clinical and genetic risk factors remain to be elucidated.

Objective To quantify the association between ambulatory COVID-19 and short-term risk of VTE, study the potential protective role of vaccination, and investigate clinical and genetic risk factors for post–COVID-19 VTE.

Design, Setting, and Participants This population-based cohort study of patients with COVID-19 from UK Biobank included participants with SARS-CoV-2 infection that was confirmed by a positive polymerase chain test reaction result between March 1, 2020, and September 3, 2021, who were then propensity score matched to COVID-19–naive people during the same period. Participants with a history of VTE who used antithrombotic drugs (1 year before index dates) or tested positive in hospital were excluded.

Exposures First infection with SARS-CoV-2, age, sex, ethnicity, socioeconomic status, obesity, vaccination status, and inherited thrombophilia.

Main Outcomes and Measures The primary outcome was a composite VTE, including deep vein thrombosis or pulmonary embolism, which occurred 30 days after the infection. Hazard ratios (HRs) with 95% CIs were calculated using cause-specific Cox models.

Results In 18 818 outpatients with COVID-19 (10 580 women [56.2%]; mean [SD] age, 64.3 [8.0] years) and 93 179 matched uninfected participants (52 177 women [56.0%]; mean [SD] age, 64.3 [7.9] years), the infection was associated with an increased risk of VTE in 30 days (incidence rate of 50.99 and 2.37 per 1000 person-years for infected and uninfected people, respectively; HR, 21.42; 95% CI, 12.63-36.31). However, risk was substantially attenuated among the fully vaccinated (HR, 5.95; 95% CI, 1.82-19.5; interaction P = .02). In patients with COVID-19, older age, male sex, and obesity were independently associated with higher risk, with adjusted HRs of 1.87 (95% CI, 1.50-2.33) per 10 years, 1.69 (95% CI, 1.30-2.19), and 1.83 (95% CI, 1.28-2.61), respectively. Further, inherited thrombophilia was associated with an HR of 2.05 (95% CI, 1.15-3.66) for post–COVID-19 VTE.

Conclusions and Relevance In this population-based cohort study of patients with COVID-19, ambulatory COVID-19 was associated with a substantially increased risk of incident VTE, but this risk was greatly reduced in fully vaccinated people with breakthrough infection. Older age, male sex, and obesity were clinical risk factors for post–COVID-19 VTE; factor V Leiden thrombophilia was additionally associated with double the risk, comparable with the risk of 10-year aging. These findings may reinforce the need for vaccination, inform VTE risk stratification, and call for targeted VTE prophylaxis strategies for unvaccinated outpatients with COVID-19.


Is There a Role for Thromboprophylaxis in Selected Outpatients With COVID-19?

Anastasios Kollias et al.

Mr Xie and colleagues1 provide important information on an understudied topic: incident venous thromboembolism (VTE) in outpatients with COVID-19. The findings of their study are commendable and provide useful conclusions. First, COVID-19 was associated with increased VTE risk, even in the outpatient setting given that a higher VTE incidence was shown among 18 818 outpatients with COVID-19 compared with 93 179 propensity score matched, noninfected participants. Second, patients with specific characteristics (older age, male sex, obesity, no/partial vaccination, and inherited thrombophilia) had higher VTE risk. Third, the VTE risk was high for up to 30 days after diagnosis. These findings are highly important and may advance case management and treatment for outpatients with COVID-19.

At present, the available data are generally against the routine use of pharmacologic thromboprophylaxis in outpatients with COVID-19.2,3 Moreover, current guidelines do not provide specific recommendations.4 However, it is common sense that selected outpatients with VTE risk factors are therefore at higher risk for disease worsening and would benefit from thromboprophylaxis on an individualized basis and after careful assessment of bleeding risk. Indeed, data show that major adverse events tend to occur early in patients hospitalized with COVID-19 who have a high-risk profile; prompt thromboprophylaxis would benefit these patients.5

The study by Mr Xie and colleagues was performed during a period when only 41% of patients with COVID-19 had been fully vaccinated; a percentage that has increased worldwide. Thus, it would be interesting to study VTE risk factors separately among the fully vaccinated group—despite VTE events having been infrequent. Moreover, apart from the patient risk factors, the disease characteristics may play a role. Symptoms that indicate disease activity or severity, ie, the duration of the fever, could be contributing to an increased VTE risk in selected patients. In addition, SARS-CoV-2 variants may exhibit a different risk regarding VTE. If these data are available, they would make for another interesting study.

Although thromboprophylaxis among outpatients with COVID-19 is not generally recommended, the data and findings derived from studies, such as this one by Mr Xie and colleagues,1 show that selected outpatients carry an increased VTE risk. On the other hand, widespread immunization, as well as the availability of the antiviral therapies, may be substantially reducing VTE risk. Whether thromboprophylaxis would benefit high-risk outpatients with COVID-19 is unclear, but it seems reasonable to conclude that an individualized strategy would improve their prognosis.


Is There a Role for Thromboprophylaxis in Selected Outpatients With COVID-19? — Reply

Junqing Xie et al.

In Reply In our recent research article regarding clinical and genetic determinants associated with venous thromboembolism (VTE) among community-dwelling patients with COVID-19,1 we reported a marked increase of 30-day VTE and identified older age, male sex, obesity, no or partial vaccination, and inherited thrombophilia as key risk factors. We appreciate the insightful comments from Prof Kollias and colleagues and their support of our call for targeted VTE thromboprophylaxis for outpatients with COVID-19.

Hospitalization is the recommended indicator for initiating antithrombotic therapy for patients with COVID-19. However, we argue that the likelihood of post−COVID-19 VTE should be conceptually seen as a continuum, with some outpatients treated for COVID-19 at an even higher risk of VTE than some hospitalized patients. Also, given that VTE hazard peaks substantially and shortly after SARS-COV-2 infection,2 individuals with COVID-19 would likely benefit from earlier interventions for primary prophylaxis. Our study1 identified several independent risk factors that can be used to stratify patients with different risk profiles for post−COVID-19 VTE. We should highlight that although existing trials (eg, ETHIC, ACTIV-4B) did not generally support routine pharmacologic thromboprophylaxis for outpatients with COVID-19, the results should be interpreted as inconclusive given the great statistical uncertainty and underrepresentation of older patients, and consequently, the low event rates. Therefore, the results do not preclude the use of thromboprophylaxis in selected outpatient subpopulations, particularly among those with a high baseline risk of VTE.3 Further trials targeting high-risk infected outpatients and more real-world studies with larger sample sizes and longer follow-up are warranted to supplement the existing evidence.4

Admittedly, the net benefits of antithrombotic therapy should always be weighed against potential harms5—eg, for those at high risk of VTE, risk of bleeding should be considered when prescribing antithrombotic therapy.6 Of note, genetic risk owing to monogenic thrombophilia or polygenic risk score, as evidenced in our study,1 was exclusively associated with venous but not arterial thromboembolism, which may be promising for identifying individuals susceptible to VTE but resistant to bleeding. Finally, we agree with the proposal from Prof Kollias and colleagues to investigate whether the risk factors persist in fully vaccinated people and what potential value disease symptoms may have for VTE prediction. However, our available data are insufficient for answering this question given the limited sample size: only 6 VTE events among the breakthrough infection cohort.

As the number of COVID-19 outpatient cases continues to increase, personalized prophylactic anticoagulation in this large population may prevent a substantial number of individuals with COVID-19 from developing severe thrombotic complications that require hospitalization and/or intensive care. The clinical and genetic risk factors identified by our study should inform the identification of participants for new research to bridge the knowledge gaps on the risk vs benefit of pharmacologic thromboprophylaxis.


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