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COVID 19 considerations in haematology

Article-COVID 19 considerations in haematology

COVID-19 can commonly be complicated with acute thrombotic events.

The virus SARS-CoV-2 commonly causes self-resolving, flu-like illnesses in most patients, but a critical illness can be seen in 5 per cent of cases – especially in the elderly population or in patients with multiple comorbidities. It causes significant cytopenia, mainly severe lymphopenia, and excessive exhaustion of CD8+ T cells, resulting in an immunocompromised state and cytokine storm. Furthermore, COVID-19 can commonly be complicated with acute thrombotic events, including venous thromboembolism, acute stroke, acute myocardial infarction, clotting of hemodialysis and extracorporeal membrane oxygenation (ECMO) catheters, and acute limb ischemia. This makes SARS-COV-2 a unique virus with an undiscovered pathophysiology.

 The most reported blood count abnormality is lymphopenia which occurs in 35-83 per cent of patients. In addition to a significant reduction in both CD4+ and CD8+ T lymphocyte subsets in COVID-19 patients, severe cases had much lower CD8+ lymphocytes and a subsequent increase positively correlated with improved clinical outcomes.

Mild thrombocytopenia has been reported in up to 20-36 per cent of COVID-19 cases however, severe thrombocytopenia is less frequent. Thrombocytopenia was independently predictive of the risk of admission to ICU, mechanical ventilation, or death. In addition, bone marrow hemophagocytosis can be a feature of severe COVID-19 and this has been observed in a small number of patients. The cytokine storm syndrome is also associated with the secondary Haemophagocytic lymphohistiocytosis (sHLH).

The diagnostic criteria of sHLH based on the H-score are fever, hepatomegaly and/or splenomegaly, 2 or 3 cytopenias, hypertriglyceridemia or hypofibrinogenaemia (or both), hyperferritinemia, serum aspartate aminotransferase elevation, hemophagocytosis on bone marrow aspirate and known immunosuppression. Laboratory tests such as elevated ferritin are useful predictors of fatality as shown in a recent retrospective, multicenter study of 150 confirmed COVID-19 cases in Wuhan, China. This report suggested that COVID-19 related mortality might be due to virally driven hyperinflammation. Neutrophil to lymphocyte ratio (NLR) has also been documented as a useful triage tool.

Patients affected with rheumatic diseases represent a particularly vulnerable group to present a severe COVID-19 associated to a sHLH, considering that they might be on immunosuppressive therapy.

In our hospital, we had a case of a 67-year-old lady; under a long-term immunosuppressive treatment (Methotrexate, Corticosteroids and Hydroxychloroquine) for her rheumatoid arthritis. She was asthmatic and hypertensive, so she had risk factors to develop a severe COVID-19 infection. Her H-Score for the diagnosis sHLH was evaluated at 200 and the probability of sHLH was 88 per cent.

Bone marrow aspiration findings were hypocellular and hemodiluted smears showed maturing myeloid and erythroid hematopoiesis, histiocytic cells with rare larger forms. No significant increase in blasts forms or dyserythropoiesis was seen. Non-hematological cells invading the bone marrow were not found.

Bone marrow biopsy yielded a very good length of evaluable marrow, which was slightly hypocellular in regard to the three cells lines with maturing trilineage hematopoiesis, relative erythroid hyperplasia and scattered macrophages (confirmed with CD68 immunohistochemical stains) showing evidence of hemophagocytosis. (Image 1)


The correlation of these findings with the clinical and laboratory tests, the negativity of blood cultures, urine culture, EBV and CMV serologies, and the H-Score at 200 points made the diagnosis of secondary hemophagocytic lymphohistiocytosis (sHLH) highly probable.

Early recognition of sHLH, a task force involving multiple specialties (rheumatologists, hematologists, intensive care physicians, infectious disease specialists, and pulmonologists) should be involved in the treatment and the follow-up of the COVID-19 patients. 

Recent data emerging from the management of patients with COVID-19 suggests an increased thrombotic tendency. Approximately one-third of patients with COVID-19 had CT scan evidence of pulmonary embolism (PE) in a French study. Notably, two thirds of the patients without PE in this cohort also had elevated D-dimers with a higher cut off value of 2660 µg/L being more predictive of PE in this cohort. From a prognostic perspective, D-dimers appear to be the most useful coagulation parameter as progressive increase in D-Dimer level is associated with the development of severe disease and in-hospital mortality.

In a study comparing coagulation parameters in hospitalised COVID-19 patients, 15 (71.4 per cent) of no survivors met the International Society on Thrombosis and Haemostasias (ISTH) criteria for overt Disseminated Intravascular Coagulation (DIC) compared with 1 (0.6 per cent) of survivors.

With recent reports of thrombotic complications in patients with COVID-19, there is increasing recognition of a distinct coagulopathy associated with COVID-19. The underlying mechanism is likely to be multifactorial including direct endothelial damage from SARS-CoV-2 or immune cells, inflammatory cytokine-induced activation of the coagulation cascade, the development of antiphospholipid antibodies and an increase in acute phase pro-coagulants such as Factor VIII and fibrinogen. Consequently, the recently published ISTH interim guidance recommends prophylactic anticoagulation with low molecular weight heparin (LMWH) for all hospitalised patients with COVID-19.

A lot is still not known about the marked difference between immune responses to SARS-CoV-2 between individuals and it is likely that genetic and environmental factors also play a role. Of particular interest is the association between certain ABO blood group genotypes and the likelihood of severe COVID-19. In a recently published genome wide association study, Blood group A and a few other Single Nucleotide Polymorphisms (SNPs) were associated with an increased risk of COVID-19-induced respiratory failure (Blood group O was apparently protective). Interestingly, Blood group A has also been shown to be associated with increased odds of thromboembolic and cardiovascular events. These findings are hardly surprising because blood group A individuals (as well as other non-O blood groups) are known to have higher plasma Von Willebrand levels and ABO blood group antigens have innate immune functions

Recently, some cases of thrombosis were also reported with a COVID-19 vaccine, the International Society on Thrombosis and Haemostasias (ISTH) recommends that all eligible adults continue to receive their COVID-19 vaccinations. At this time, the small number of reported thrombotic events relative to the millions of administered COVID-19 vaccinations does not suggest a direct link, the ISTH believes that the benefits of COVID-19 vaccination strongly outweigh any potential complications even for patients with a history of blood clots or for those taking blood thinning medications.

Therefore, monitoring of hematological parameters such as the absolute lymphocyte count, neutrophil-to-lymphocyte ratio and D-dimers can offer prognostic insight in the management of COVID-19 and will help with early identification of the high-risk group of patients requiring more intensive care.

References available on request

Photo Kayane Mheidly.jpg

Dr Kayane Mheidly

This article appears in the latest issue of Omnia Health Magazine. Read the full issue online today.

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