The Interplay of Inflammation and Coagulation in COVID-19 Patients Receiving Extracorporeal Membrane Oxygenation Support

Objective Bleeding and thrombosis are common complications during Extracorporeal Membrane Oxygenation (ECMO) support for COVID-19 patients. We sought to examine the relationship between inflammatory status, coagulation effects, and observed bleeding and thrombosis in patients receiving venovenous (VV) ECMO for COVID-19 respiratory failure. Study Design Cross-sectional cohort study Settings Quaternary care institution. Patients The study period from April 1, 2020, to January 1, 2021, we included all patients with confirmed COVID-19 who received VV ECMO support. Intervention None. Measurements and Main Results Thirty-two patients were supported with VV ECMO during the study period, and 17 patients (53%) survived to hospital discharge. The ECMO nonsurvivors mean lactate dehydrogenase (LDH) levels were markedly elevated in comparison to survivors (1046 u/L [IQR = 509, 1305] vs 489 u/L [385 658], p = 0.003). Platelet/fibrinogen dysfunction, as reflected by the low Maximum Amplitude (MA) on viscoelastic testing, was worse in nonsurvivors (65.25 mm [60.68, 67.67] vs 74.80 mm [73.10, 78.40], p = 0.01). Time-group interaction for the first seven days of ECMO support, showed significantly lower platelet count in the nonsurvivors (140 k/ul [103, 170] vs 189.5 k/ul [ 146, 315], p < 0.001) and higher D-dimer in (21 μg/mL [13, 21] vs 14 μg/mL [3, 21], p < 0.001) in comparison to the survivors. Finally, we found profound statistically significant correlations between the clinical markers of inflammation and markers of coagulation in the nonsurvivors group. The ECMO nonsurvivors experienced higher rate of bleeding (73.3% vs 35.3%, p = 0.03), digital ischemia (46.7% vs 11.8%, p = 0.02), acute renal failure (60% vs 11.8%, p = 0.01) and bloodstream infection (60% vs 23.5%, p = 0.03). Conclusion The correlation between inflammation and coagulation in the nonsurvivors supported with VV ECMO could indicate dysregulated inflammatory response and worse clinical outcomes.

Magnetic Resonance Angiography of the Hand Vasculature in Patients With Systemic Sclerosis and Systemic Lupus Erythematosus

Background: When patients with systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) develop digital ischemia, conventional angiography (CA) is traditionally used to assess hand vasculature. Recently, Chang et al described an angiographic classification system for patients with SSc. Conventional angiography uses intravascular contrast agents that are nephrotoxic and vasoconstrictive. Owing to these limitations, this study assesses the use of contrast-enhanced magnetic resonance angiography (MRA) as an alternative to CA to evaluate hand vasculature in patients with digital ischemia. Methods: This retrospective case series reports on 38 contrast-enhanced MRAs of hand vasculature from 30 symptomatic patients with SSc (N = 21) or SLE (N = 9). The radial and ulnar arteries (RA, UA) and the superficial and deep palmar arches were evaluated at standard reference points both quantitatively and qualitatively for their diameter, patency, and Chang classification. Results: In SSc MRAs (n = 26), the UA was significantly smaller than the RA and was occluded in 46%. In SLE MRAs (n = 12), the UA and RA had no difference in diameter and the UA was occluded in 25%. In SSc, the most common Chang classification was type 2 (UA involvement) in 44%. In SLE, the most common Chang classification was type 4 (UA and RA involvement) in 45%, with 18% classified as type 2. Conclusions: Contrast-enhanced MRA used to assess hand vasculature in SSc patients with digital ischemia shows similar patterns of vascular involvement as previously demonstrated by CA. While vascular involvement in SSc predominantly involves the UA, the RA is also frequently involved in SLE.

Sensory-Motor Polyneuropathy and Digital Ischemia: A Rare Presentation of Granulomatosis with Polyangiitis

Granulomatosis with polyangiitis (GPA) typically presents with upper or lower respiratory tract symptoms and/or with renal involvement. Although it can affect the peripheral nervous system frequently, with mononeuritis multiplex being the most common pattern, the occurrence of peripheral sensory-motor polyneuropathy as a presenting manifestation is distinctly rare. Prevalence of digital gangrene is also extremely rare in GPA. We describe a 46-year-old woman presenting with severe peripheral sensorimotor polyneuropathy affecting bilateral lower limbs preceded by a purpuric skin rash and multiple painful ulcers confined to the lower limbs. She had evidence of digital ischemia affecting multiple toes and dry gangrene of the left 4th toe. Diagnosis of GPA was made based on skin biopsy, positive ANCA serology, and clinical criteria. She made a good recovery following aggressive immunosuppressive treatment with methylprednisolone and cyclophosphamide and was maintained on prednisolone and azathioprine. This case highlights the importance of suspecting GPA in a patient presenting with sensorimotor polyneuropathy and/or digital ischemia even in the absence of more classic presenting features and underlies the necessity of accurate differential diagnosis in evaluating a case of peripheral neuropathy.

Digital gangrene as an unusual paraneoplastic manifestation of hodgkins lymphoma—a rare case report

Background Hodgkin’s lymphoma presenting with digital ischemia and gangrene is a rare manifestation. Paraneoplastic manifestations are rare in Hodgkin’s lymphoma but can occur in the form of paraneoplastic cerebellar degeneration (PCD) and dermatomyositis/polymyositis. This case report adds an exceptional presentation of Hodgkin's lymphoma as digital ischemia and gangrene. Case presentation We report a case of a 60-year-old male patient who presented with fever, cough, shortness of breath, the pain in the right middle finger. On examination bluish-black discoloration of the right middle finger, left middle finger, ring finger, and generalized lymphadenopathy was noted. On further evaluation, he was found to have anemia, eosinophilia, and severe thrombocytopenia with a normal coagulation profile and negative rheumatological workup. Arterial Doppler of both upper limbs showed the normal study. He was diagnosed to have Hodgkin’s lymphoma on the lymph node and bone marrow biopsy. He was started on chemotherapy with partial improvement in symptoms and was lost to follow-up after 2 cycles. Conclusions Digital ischemia can be a rare paraneoplastic manifestation of Hodgkin’s lymphoma.

Considerations When Performing Arthrodesis in the Scleroderma Hand

Background Hand deformities secondary to scleroderma can limit activities of daily living and be associated with substantial disability. This study aimed to evaluate the outcomes following arthrodesis performed to treat digital contractures secondary to scleroderma. Methods We performed a retrospective review of all patients with scleroderma who underwent arthrodesis by a single surgeon from 2015 to 2020. We collected demographic information, operative variables, and outcomes variables. Our primary outcome was occurrence of any postoperative complication, which we defined to include wound dehiscence, digital ischemia, malunion, nonunion, cellulitis, and osteomyelitis. We calculated descriptive statistics and performed all analyses at the joint level. Results We identified 9 patients who underwent arthrodesis of 19 joints. All patients were women with a mean age of 55.3 years. At the time of surgery, most patients were taking disease-modifying antirheumatic drugs (DMARDs). Kirschner wires (K-wires) were used in most cases (n = 18), 15 of which were removed uneventfully at an average of 4.8 months after surgery. With a mean follow-up time of 15.4 months, the overall complication rate was 5.3% (n = 1). This patient developed digital ischemia in 1 of 4 operative digits, which became gangrenous and required amputation. Conclusions Our study suggests that arthrodesis can be performed safely in the scleroderma hand, even when patients are taking DMARDs. Given the uneventful K-wire removal in all joints and the high risk of exposure of buried hardware in this population, we recommend nonpermanent placement of K-wires. Hand surgeons may consider arthrodesis in the scleroderma hand before proceeding to revision amputation.

Outcomes of periarterial sympathectomy in patients with digital ischemia

Introduction Digital ischemia with subsequent severe pain and tissue loss is often difficult to treat, with no obvious guidelines or strong evidence in the literature to support a specific treatment modality. Patients who fail medical treatment remain with very limited surgical options due to the difficulty of any intervention in this “no man’s land” area of the hand, as described since 1918. Extended distal periarterial sympathectomy is reported as an effective treatment option since the eighties of last century. The procedure entails large incisions and major technical difficulties. In this study, we describe a less invasive approach with very promising results and equally high success rates. Materials and Methods This was a prospective study. All patients with severe digital ischemia manifesting with bluish discoloration, ulceration, and/or dry gangrene who failed medical treatment underwent distal periarterial sympathectomy for the radial and ulnar arteries, with added digital sympathectomy in very severe cases. Primary endpoints were ulcer healing and improvement in pain scores assessed by Visual Analog Scale pain scoring system. Secondary endpoints included complications and amputation rates. Results This study recruited 17 patients between January 2019 and January 2020. The mean follow-up was 14.6 months. The mean age was 33.71 (±SD 13.14) years. 41% were males. 59% suffered from vasculitis, 35% of patients had dry gangrene, and 71% had ulcers. Periarterial radial and ulnar sympathectomy was performed for all cases, with digital sympathectomy for 12 fingers. We had 50% complete ulcer healing within 1 month ( p = 0.031), and 100% were completely healed at 6 months ( p < 0.001). Pain scores showed significant reductions at 1 ( p = 0.001) and 6 months ( p < 0.001) of follow-up. Conclusion Distal periarterial sympathectomy demonstrates high success rates in terms of pain relief and ulcer healing in severe digital ischemia.

Patient with H syndrome, cardiogenic shock, multiorgan infiltration, and digital ischemia

Background H syndrome (HS) is a rare autoinflammatory disease caused by a mutation in the solute carrier family 29, member 3 (SCL29A3) gene. It has a variable clinical presentation and little phenotype-genotype correlation. The pathognomonic sign of HS is cutaneous hyperpigmentation located mainly in the inner thighs and often accompanied by other systemic manifestations. Improvement after tocilizumab treatment has been reported in a few patients with HS. We report the first patient with HS who presented cardiogenic shock, multiorgan infiltration, and digital ischemia. Case presentation 8-year-old boy born to consanguineous parents of Moroccan origin who was admitted to the intensive care unit during the Coronavirus Disease-2019 (COVID-19) pandemic with tachypnoea, tachycardia, and oliguria. Echocardiography showed dilated cardiomyopathy and severe systolic dysfunction compatible with cardiogenic shock. Additionally, he presented with multiple organ dysfunction syndrome. SARS-CoV-2 polymerase chain reaction (PCR) and antibody detection by chromatographic immunoassay were negative. A previously ordered gene panel for pre-existing sensorineural hearing loss showed a pathological mutation in the SCL29A3 gene compatible with H syndrome. Computed tomography scan revealed extensive alveolar infiltrates in the lungs and multiple poor defined hypodense lesions in liver, spleen, and kidneys; adenopathy; and cardiomegaly with left ventricle subendocardial nodules. Invasive mechanical ventilation, broad antibiotic and antifungal coverage showed no significant response. Therefore, Tocilizumab as compassionate use together with pulsed intravenous methylprednisolone was initiated. Improvement was impressive leading to normalization of inflammation markers, liver and kidney function, and stabilising heart function. Two weeks later, he was discharged and has been clinically well since then on two weekly administration of Tocilizumab. Conclusions We report the most severe disease course produced by HS described so far in the literature. Our patient’s manifestations included uncommon, new complications such as acute heart failure with severe systolic dysfunction, multi-organ cell infiltrate, and digital ischemia. Most of the clinical symptoms of our patient could have been explained by SARS-CoV-2, demonstrating the importance of a detailed differential diagnosis to ensure optimal treatment. Although the mechanism of autoinflammation of HS remains uncertain, the good response of our patient to Tocilizumab makes a case for the important role of IL-6 in this syndrome and for considering Tocilizumab as a first-line treatment, at least in severely affected patients.