key: cord-0689017-7s4x5v1k
authors: Schultz, Kathryn; Wolf, Jennifer Moriatis
title: Digital Ischemia in COVID-19 Patients: Case Report
date: 2020-04-30
journal: J Hand Surg Am
DOI: 10.1016/j.jhsa.2020.04.024
sha: ebb91b37009eaa9277f18e46ca1595f1b7223d6f
doc_id: 689017
cord_uid: 7s4x5v1k

Abstract As COVID-19 continues to cause immense burden on global healthcare systems, it is crucial to further understand the breadth of this disease process. Recent reports have identified hypercoagulability in a subset of critically ill patients and extremity ischemia in an even smaller cohort. As abnormal coagulation parameters and extremity ischemia have been shown to correlate with poor disease prognosis, understanding how to treat these patients is crucial. In order to better describe the identification and management of this phenomenon, we present two cases of critically ill patients with COVID-19 who developed fingertip ischemia while in the intensive care unit.

30 COVID-19, the disease caused by the 2019 novel coronavirus, has placed an unprecedented 31 strain on global health care systems. While the disease is known predominantly for its respiratory 32 manifestations, a subset of critically ill patients demonstrates clinically significant 33 hypercoagulability. [1] [2] [3] This phenomenon has been noted by multiple intensive care unit (ICU) 34 physicians and has been further described at the Tongji Hospital in Wuhan, China. 1, 2 Thrombotic 35 events range from acute pulmonary embolism in patients with COVID-19 pneumonia to 36 extremity ischemia, and the precise incidence of thrombotic events has yet to be determined. 3-6 37

As our understanding of this disease grows, it is crucial to investigate this trend further because 38 hypercoagulability may worsen disease prognosis in critically ill COVID-19 patients. 3,7 39 40 Few studies to date have focused exclusively on patients with signs of hypercoagulability. An 41 early analysis from Wuhan, China described seven cases of extremity ischemia in critically ill 42 patients with COVID pneumonia. 1 All 7 of these patients, who did not meet criteria for shock 43 and were not undergoing active therapy with vasopressors, demonstrated varying degrees of 44 acral ischemia; the most common manifestations of such ischemia included plantar plaques and 45 acrophytic bruises. 1 Notably, the authors identified a relationship between disease aggravation 46 and the presence of ischemia. 1 Institutional review board approval was obtained for deidentified presentation of patient data and 60 images. 61

A 70-year-old female with no known past medical history presented to the emergency 63 department (ED) with a one-week history of fevers, chills, worsening shortness of breath, 64 headache, and malaise. Several days prior she had tested negative for COVID-19 at an outside 65 hospital, but presented to our facility secondary to worsening symptoms. Upon arrival to the ED 66 her vitals included a temperature of 36.7°C, pulse of 101 bpm, respiratory rate of 26 breaths per 67 minute, and an oxygen saturation of 88% on room air. While in the emergency department she 68 required oxygen at 6L/min via nasal cannula. The initial chest x-ray demonstrated perihilar 69 opacification. She tested PCR positive for COVID-19 and was subsequently admitted to the ICU 70 for management of acute hypoxemic respiratory failure secondary to acute respiratory distress 71 syndrome (ARDS) and COVID-19. The patient was intubated shortly thereafter due to increasing 75 Approximately 12 days following presentation to the ED, the patient developed gradually 76 worsening duskiness of the right second, third, and fourth fingertips while in the ICU. Notably, 77 the patient had had three arterial line placements on the left side (one radial, two brachial), but 78 none on the right side. The hand service was consulted and the physical examination showed a 79 mottled, dusky appearance to the distal phalanges and nailbeds of the index, middle, and ring 80 fingers. The fingers were also noted to be cool to palpation and Doppler signals were absent at The patient's fibrinogen (486 mg/dL) was also elevated 3 days prior to consultation. 88 89 Based on this presentation, the orthopaedic service recommended the continuation of the 90 patient's 25,000-unit heparin drip at 11 units/kg/hour (previously prescribed empirically 91 secondary to elevated D-dimer and then continued for a right femoral DVT) in addition to duplex 92 studies and thermal warming of the affected limb. Application of topical nitroglycerin to the 93 affected area was also recommended. 8 Results of the arterial duplex ultrasound demonstrated 94 patent brachial, radial, and ulnar arteries without evidence of hemodynamically significant Throughout the hospital course, the digital ischemia remained stable. Other notable events 98 include septic shock, severe ARDS, acute kidney injury, obstructive shock secondary to 99 mechanical ventilation and intermittent vasopressor use. Other medical therapies included 100 tocilizumab, kaletra/ribavirin, cefepime, vancomycin, hydroxychloroquine, azithromycin, 101 cefdinir, ceftriaxone, oral vancomycin and metronidazole. Due to worsening clinical status, the 102 decision was made to pursue comfort care and the patient ultimately died. 103

A 43-year-old male with a past medical history of obesity, hypertension, and hyperlipidemia 106

presented to the ED with shortness of breath, cough, and chest pain that had been progressively 107 worsening over the past week. The patient also reported fatigue, diarrhea, and decreased urine 108 Digital ischemia, likely of subacute duration, was diagnosed (Figures 1-2) . The hand surgery 127 service recommended forearm and hand warming in addition to topical nitroglycerin 128 application. 8 Given the recent hemorrhage, anticoagulation was a relatively contraindicated; 129 however given stable hemoglobin measurements, volar pulp discoloration, and a concern for 130 embolic phenomena, low-dose heparin was recommended and was initiated one day following 131 consult recommendation. Notably, however, patient A only had 5 days between ischemia and death whereas patient B 164 demonstrated tissue improvement over a 2-week time period. Therefore, we recommend the 165 rapid institution of an appropriate anticoagulation regimen for the treatment of this phenomenon, with consideration for prophylactic anticoagulation given the observed incidence of deep venous 167 thromboses in these patients and others. 9 Another possibility for the ischemic phenomenon is 168 vasopressor use; however it is unlikely that vasopressors would cause unilateral ischemia. perhaps the cause of, thrombotic events such as those described in this report. 2 While we were 175 unable to test these patients for such antibodies, we acknowledge this hypothesis as a potential 176 explanation for the ischemic events in these two patients. 177

The relationship between coagulopathy and poor disease prognosis in COVID-19 patients merits 178

discussion. Several studies have demonstrated that patients showing abnormal coagulation 179 studies and those with acral ischemia are at an increased risk of a poor prognosis. 1, 7, 9, 10 For 180 instance, Guan and colleagues showed that patients with elevated D-dimer were more likely to 181 have severe disease requiring ICU admission and mechanical ventilation, or to die. 7 Additionally, 182

Tang et al. claimed that patients with COVID-19 pneumonia who had significantly higher D-183 dimers and fibrinogen degradation products as well as longer PTs at admission were more likely 184 to die than those without these abnormal parameters. 10 Interestingly, while both of our patients 185 demonstrated elevated D-dimer levels, patient A's first D-dimer following admission was only 186

Based on the clinical course of these two COVID-19 patients, we hypothesize that 189 coagulopathies, especially those of the hand, are a marker of significant illness and merit close 190 monitoring and early hand service consultation for appropriate intervention. It is critical to 191 monitor for thromboembolic events in the extremities of critically ill patients to avoid permanent 192 damage and/or limb loss. 

Clinical analysis of seven cases of critical new coronavirus 207 pneumonia complicated with extremity ischemia

Coagulopathy and antiphospholipid antibodies in patients 210 with Covid-19

Characteristics, causes, diagnosis and treatment of coagulation dysfunction 212 in patients with COVID-19

COVID-19 Complicated by acute pulmonary embolism

Incidence of thrombotic complications in 216 critically ill ICU patients with COVID-19

Acute pulmonary embolism and COVID-19 218 pneumonia: a random association?

Clinical Characteristics of 2019 Novel Coronavirus Infection in

Reduced perfusion in systemic sclerosis digital ulcers 222 (both fingertip and extensor) can be increased by topical application of glyceryl trinitrate

Causes and outcomes of finger ischemia in 225 hospitalized patients in the intensive care unit

Abnormal coagulation parameters are associated with poor 227 prognosis in patients with novel coronavirus pneumonia