COVID-19: systemic disease with significant hematological bias

Publicação: 11 de June de 2020

Shortage of dialysis kits and fluids due to COVID-19 raises concern

ICNARC reported that 1 in 5 severely ill coronavirus patients requires renal replacement therapy for an average of 4 days

In view of the COVID-19 pandemic, several aspects have been studied in an attempt to better understand the disease and, thus, reduce the number and severity of infected individuals. As it is a recent disease with nearly daily changes in events and knowledge, it is not yet certain of all the possible repercussions of SARS-CoV-2 infection in hematological diseases, so that there are no definite and absolute answers to the moment. However, there are already serious recommendations from the main hematology societies in the world (American, European and Brazilian), which vary widely according to each pathology. In addition, many studies have been published. However, data on COVID-19 in people with hematological diseases are scarce.

An American Journal of Hematology study entitled “Hematologic parameters in patients with COVID 19 infection”, published in March, analyzed 69 patients admitted to the National Center for Infectious Diseases (NCID) in Singapore, in order to observe the most frequent and relevant changes in the blood picture, caused by infection by the coronavirus. Approximately 13% of the cases required treatment in the Intensive Care Unit (ICU), whose average age was 12 years older than that of the group of individuals who did not need a place in the Intensive Care Unit (ICU). The study on hematological parameters in patients with COVID-19 infection showed that during admission, most patients had a complete blood count (hemoglobin, leukocytes and platelet count) and lactate dehydrogenase (LDH). In addition, no patient had moderate or severe thrombocytopenia, which is often seen in other viral diseases, such as dengue. Upon admission, leukopenia was observed in 19 patients (29.2%), being severe (< 2,000/mm³) in only one individual. Lymphopenia was observed in 24 patients (36.9%) of the CBC: moderate (<1.000/mm³) in 79.2% of the cases and severe (<500/mm³) in the remaining 20.8% Platelet counts were found to be normal in 80% of individuals and slightly reduced (between 100,000 and 150,000/mm³) in other cases. Peripheral blood smear observation revealed the presence of reactive lymphocytes in most lymphopenia patients.

Also, according to the survey, in general, those infected who required transfer to the ICU had lower lymphocyte counts than the others (median 400/mm³ in the ICU group x 1,200/mm³ in the other group). This finding corroborates with evidence from previous studies, which pointed out lymphopenia as a factor of poor prognosis. Lymphopenia <600/mm³ can be considered an indicator for early ICU admission. The research also reveals that during hospitalization in the ICU, patients showed a decrease in hemoglobin, lymphocyte and monocyte values, when compared to the other group. Regarding neutrophils, there was greater neutrophilia in the blood counts of the ICU group. The platelet count did not suffer great variations during the evolution of the individuals, regardless of the place of hospitalization (ICU or not). It is noteworthy that in the analyzed population, advanced age and lymphopenia were associated with a worse prognosis.

Laboratory changes in patients with COVID-19

Serological tests will be essential to detect specific IgG antibodies against the virus in an already exposed and asymptomatic population, thus allowing an epidemiological investigation and the identification of asymptomatic carriers. In relation to laboratory changes in patients with COVID-19, some hematological parameters can help in predicting and monitoring disease progression to more severe conditions. Already described in the worldwide guidelines; we can mention the blood count, blood coagulation test, plasma fibrinogen, D-dimer, ferritin, triglycerides, among others. Some hematological parameters can assist in predicting and monitoring disease progression for more severe conditions:

According to studies, a significant increase in monocyte cell volume (MDW, an innovative parameter available in a few models of hematological equipment) was observed, especially in patients with worse clinical conditions. Coagulation tests are very important, as increased prothrombin time and D-dimer levels are significant predictors of disease severity and reinforce the possibility of disseminated intravascular coagulation (DIC) as one of the most serious complications in infection by SARS-CoV-2.

Among the hematological complications resulting from Covid, there are basically thromboembolic phenomena resulting from a disseminated intravascular coagulopathy and hemophagocytic lymphohistiocytosis, secondary to viral damage and immune response.

Increased demand for dialysis causes concern of supply shortage

A recently published study entitled “COVID-19: increasing demand for dialysis sparks fears of supply shortage” points out that more than a quarter of patients with COVID-19 requiring ventilation also need renal support in the form of dialysis, raising concerns that significant disposable supply problems may occur including necessary filtrate and and plastic consumables. According to Dr. Graham Lipkin, a nephrology consultant, is a little-recognized challenge. “Although the original focus was on the fact that we have enough ventilators and intensive care beds, it became evident that there is a high incidence of acute kidney injury (AKI), requiring some form of renal replacement therapy (RRT) through dialysis. Considering the number of people entering intensive care, there are increasing capacity challenges across the system”, he warns.

Dr. Lipkin explains that patients in intensive care usually receive continuous venous-venous hemofiltration dialysis, which requires a machine and plastic disposables together with the dialyzer and filtrate replacement fluids. According to him, given the growing demand in the UK, Europe and especially in the USA, disposables and fluid are in short supply. “When patients with COVID-19 arrive at the hospital, they are usually dehydrated due to prolonged fever and because they do not eat or drink normally. There appears to be a direct viral invasion of the kidney, affecting the renal tubules and podocytes. Severe COVID-19 is associated with a ‘cytokine storm’ and, throughout this inflammation, the kidneys are victims”, describes Dr. Lipkin.

In April, groups of patients expressed concern about reports of a critical shortage of supplies for the provision of dialysis treatment in the ICU for people with acute kidney injury caused by SARS-CoV-2. The Medicines and Healthcare products Regulatory Agency (MHRA) and the National Health Service of England (NHS) have warned of a severe interruption in the supply of kits and fluids to carry out continuous vein-to-vein hemofiltration, including hemodiafiltration (CVVH and CVVHD). The alert explained that patients appeared to have a hypercoagulopathy that was causing CVVH and CVVHD clots, before the filter and inside the filter reducing further disposable availability. The National Center for Auditing and Research in Intensive Care (ICNARC) reported that one in five patients with severely ill coronavirus needs renal replacement therapy (RRT) for an average of 4 days, rising to 28.8% among patients who require advanced respiratory support after hospitalization because of SARS-CoV-2. There is significant global pressure on the supply of types of renal replacement therapies and is being used to treat patients with COVID-19 who develop kidney problems.

Increased clots in patients with COVID-19

Recently, doctors have noted that the increased risk for clot formation and thrombosis has been increasingly frequent, especially in patients who develop the severe form of COVID-19. Article published in the Journal of the American College of Cardiology entitled “COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy, and Follow-up”, signed by experts from more than 30 hospitals around the world, states that the inflammation caused by SARS-CoV-2 in the body is one of the factors that leads to a greater tendency in the formation of thrombi and thromboembolism. It is known that the virus has an influence on increased coagulation, but it is not yet known exactly how. One of the possibilities raised is that the virus uses receptors called ACE2 to enter the human body. These receptors are generally found in the endothelium (a type of tissue that lines blood vessels (such as arteries and veins) and the inner part of the heart and which influences the control of coagulation. Another possibility that has been widely debated is the issue of the so-called “cytokine storm”. These proteins are known to send messages to cells and to modulate the attack organized by the immune system to the body’s invading virus, creating an inflammatory condition in the body. One of the responses to the inflammatory process is precisely the increase in blood clotting. The problem is that, in SARS-CoV-2, infection, some patients have an excessive production of these cytokines, increasing the inflammatory response and the rate of coagulation.

It is a great uncertainty how big the burden that SARS-CoV-2 infection will cause in the health of each country. Health professionals and hospital managers work daily to try to minimize the effects of treatment interruptions and patients’ illness, including the most susceptible, such as the elderly and the immunosuppressed.

Learn more:

Intensive Care National Audit and Research Centre. ICNARC report on COVID-19 in critical care.

NHS England. Clinical guide for renal replacement therapy options in critical care during the coronavirus pandemic.

NHS England. Clinical guide for acute kidney injury in hospitalised patients with COVID-19 outside the intensive care unit during the coronavirus pandemic.

Eleven Faces of Coronavirus Disease 2019.

Diagnostic Utility of Clinical Laboratory Data Determinations for Patients with the Severe COVID-19.

Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.

Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: A meta-analysis.

The critical role of laboratory medicine during coronavirus disease 2019 (COVID-19) and other viral outbreaks.

Clinical Features and Treatment of COVID‐19 Patients in Northeast Chongqing.

Clinical Features of 69 Cases with Coronavirus Disease 2019 in Wuhan, China.

Novel Coronavirus (COVID19) Situation Report-23.

Alterações laboratoriais em pacientes com COVID-19.

Shortage of Dialysis Kits and Fluids Due to COVID-19.