Cutaneous Clues Linked to COVID-19 Coagulation Risk

Damian McNamara

August 05, 2020

Editor's note: Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.

Skin eruptions could help physicians identify people with severe COVID-19 who are more likely to develop coagulopathies, new evidence suggests.

Researchers at Weill Cornell Medicine NewYork-Presbyterian Medical Center in New York City linked livedoid and purpuric skin eruptions to a greater likelihood for occlusive vascular disease associated with SARS-CoV-2 infection in a small case series.

These skin signs could augment coagulation assays in this patient population. "Physicians should consider a hematology consult for potential anticoagulation in patients with these skin presentations and severe COVID-19," senior author Joanna Harp, MD, told Medscape Medical News.

"Physicians should also consider D-dimer, fibrinogen, coagulation studies, and a skin biopsy given that there are other diagnoses on the differential as well."

The research letter was published online today in JAMA Dermatology.

The findings build on multiple previous reports of skin manifestations associated with COVID-19, including a study of 375 patients in Spain. Among people with suspected or confirmed SARS-CoV-2 infection, senior author of the Spanish research, Ignacio Garcia-Doval, MD, PhD, also observed livedoid and necrotic skin eruptions more commonly in severe disease.

"I think that this case series [from Harp and colleagues] confirms the findings of our previous paper — that patients with livedoid or necrotic lesions have a worse prognosis, as these are markers of vascular occlusion," he told Medscape Medical News.

Harp and colleagues report their observations with four patients aged 40 to 80 years. Each had severe COVID-19 with acute respiratory distress syndrome and required intubation. Treating clinicians requested a dermatology consult to assess acral fixed livedo racemosa and retiform purpura presentations.

D-dimer levels exceeded 3 micrograms/mL in each case. All four patients had a suspected pulmonary embolism within 1 to 5 days of the dermatologic findings. Prophylactic anticoagulation at admission was changed to therapeutic anticoagulation because of increasing D-dimer levels and the suspected thrombotic events.

"I think that the paper is interesting because it shows the associated histopathological findings and has important clinical implications due to the association with pulmonary embolism," said Garcia-Doval, a researcher at the Spanish Academy of Dermatology in Madrid. "These patients should probably be anticoagulated."

Skin Biopsy Results

Punch biopsies revealed pauci-inflammatory thrombogenic vasculopathy involving capillaries, venules, arterioles, or small arteries.

Livedo racemosa skin findings point to partial occlusion of cutaneous blood vessels, whereas retiform purpura indicate full occlusion of cutaneous blood vessels.

An inability to confirm the exact timing of the onset of the skin rash was a limitation of the study.

"The findings suggest that clinicians caring for patients with COVID-19 should be aware of livedoid and purpuric rashes as potential manifestations of an underlying hypercoagulable state," the authors note. "If these skin findings are identified, a skin biopsy should be considered because the result may guide anticoagulation management."

Observations During an Outbreak

The researchers observed these cases between March 13 and April 3, during the peak of the COVID-19 outbreak in New York.

"We did see additional cases since our study period. However, it has decreased significantly with the falling number of COVID-19 cases in the city," said Harp, a dermatologist at NewYork-Presbyterian.

Another contributing factor in the drop in cases was "implementation of earlier, more aggressive anticoagulation in many of these patients at our institution," she added.

The investigators plan to continue the research. "We are working on a more formalized study," lead author Caren Droesch, MD, told Medscape Medical News.

"But given very low patient numbers in our area we have not started recruiting patients," said Droesch, a resident at Weill Cornell Medicine and NewYork- Presbyterian at the time of the study. She is now a dermatologist at Mass General Brigham in Wellesley, Massachusetts.

Consider a Dermatology Consult

"This is a small case series of four patients, but mirrors what we have seen at our institution and what others have reported about individual patients around the world," Anthony Fernandez, MD, PhD, a dermatologist at Cleveland Clinic in Ohio, told Medscape Medical News. "The skin, like many other organ systems, can be affected by thrombotic events within the setting of COVID-19 disease."

Similar to the current study, Fernandez observed skin manifestations in people with severe COVID-19 with elevated D-dimer levels. These patients typically require mechanical ventilation in the intensive care unit, he added.

"As these authors point out, it is important for all clinicians caring for COVID-19 patients to look for these rashes," said Fernandez, who coauthored a report on skin manifestations in this patient population. "We also agree that clinicians should have a low threshold for consulting dermatology. A skin biopsy is minimally invasive and can be important in confirming or refuting that such rashes are truly reflective of thrombotic vasculopathy."

Harp, Droesch and Garcia-Doval have disclosed no relevant financial relationships. Fernandez received funding from the Clinical and Translational Science Collaborative at Case Western Reserve University to study skin manifestations of COVID-19.

JAMA Derm. Published online August 5, 2020. Research Letter

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