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Vascular calcifications and calciphylaxis in a patient on concurrent haemodialysis and Coumadin therapy
  1. Jack Schnur,
  2. Hadeer Sinawe,
  3. Athina Lidia Yoham and
  4. Damian Casadesus
  1. Internal Medicine, Jackson Memorial Hospital, Miami, Florida, USA
  1. Correspondence to Dr Damian Casadesus; dcasadesus{at}


Calciphylaxis is a rare life-threatening condition, with calcification of small and medium-sized vessels leading to skin necrosis. It has a high morbidity and mortality, and most of the patients die from wound superinfection and sepsis. A 48-year-old man with a history of end-stage renal disease on haemodialysis and Coumadin therapy for venous thromboembolism presented with pulmonary oedema after missing two haemodialysis treatment. At examination, he had bilateral lower extremity dark brown, possibly necrotic, painful ulcers. He was diagnosed with calciphylaxis and treated with sevelamer hydrochloride, low calcium dialysate and sodium thiosulfate with haemodialysis. He received daily wound care with topical collagenase. After daily wound care treatment for 4 months, the patient’s ulcers completely healed. The patient had been followed for 8 months, which included 29 additional readmissions, 3 admissions related to bacteraemia and 26 admissions with the diagnosis of pulmonary oedema and hyperkalaemia requiring haemodialysis.

  • renal system
  • skin
  • medical management
  • dialysis

Statistics from


Calcific uraemic arteriolopathy (CUA), or calciphylaxis, is a rare life-threatening condition characterised by the calcification of small and medium-sized vessels leading to skin necrosis. Risk factors for calciphylaxis include end-stage renal disease on haemodialysis, female sex, obesity, hypercalcaemia, elevated alkaline phosphatase, hypercoagulable state, malignancy and medications such as chemotherapy, vitamin D and Coumadin.1–4 The patient usually presents with bilateral, painful, non-healing, skin ulcers that can resemble other medical conditions that develop into ischaemic necrotic lesions with acral gangrene.

CUA has a poor prognosis with a high morbidity and mortality. Sepsis has been the leading cause of death in 41%–58% of patients with calciphylaxis.5 6 The estimated disease-specific survival rate for calciphylaxis 1 year after diagnosis is 45.8%.6 We present a patient with end-stage renal disease on haemodialysis, Coumadin for venous thromboembolism, normal calcium levels and non-healing ulcers of the lower extremities, the wounds of which healed completely after 4 months of treatment.

Case presentation

The patient is a 48-year-old man with a medical history of end-stage renal disease on haemodialysis for 1 year, heart failure with preserved ejection fraction, hypertension and thrombosis of the right common and superficial femoral veins on Coumadin who presented to the hospital due to dyspnoea. The patient had a history of inconsistent haemodialysis and non-compliance with medications. His last haemodialysis was approximately 3 days before presentation. The patient also complained of lower extremity oedema associated with bilateral painful ulcers for 1 month. He is a lifetime non-smoker and does not use recreational drugs or alcohol. The family medical history was significant for a maternal grandmother with diabetes mellitus type 2.

At admission, the vital signs were blood pressure of 192/133 mm Hg, heart rate of 84/min, respiratory rate of 18/min and oxygen saturation of 99% on ambient air. On physical examination, the patient had a regular heart rate and bilateral lung crackles. The skin examination showed a right leg with a full-thickness wound approximately 16×12 cm with scattered dark brown, necrotic, painful, stellated and sharply demarcated ulcers (figure 1). The left leg showed an ulcer with similar characteristics approximately 10×4 cm.

Figure 1

Brown, painful, stellate, necrotic, demarcated ulcer of the right lower extremity.


The laboratory studies showed parathyroid hormone of 1252 pg/mL, corrected calcium of 9.6 mg/dL, 25-hydroxy vitamin D of 33.0 ng/mL and phosphorus of 5.7 mg/dL. Chest radiograph revealed acute pulmonary oedema. A CT angiogram of the chest revealed mild to moderate coronary artery calcifications and intimal calcification of the ascending thoracic aorta. A skin biopsy with von Kossa stain showed stippling in the adipocyte membranes and calcified atherosclerosis of medium-sized blood vessels in the dermis, confirming the diagnosis of calciphylaxis.


The patient underwent emergent haemodialysis, and his respiratory symptoms resolved. The Coumadin was discontinued and he was started on Eliquis for deep venous thrombosis. The patient was continued on sevelamer hydrochloride and a low phosphorus diet. Low calcium dialysate and sodium thiosulfate were initiated with haemodialysis, as well as vitamin D replacement.

Regarding the patient’s wounds, the primary goals of wound care are to remove the necrotic tissue and to prevent an infection. Enzymatic debridement was applied in our patient’s wound care.2 7 The wounds were cleaned daily with normal saline, and collagenase was applied to the ulcers. The ulcerative areas were covered with a non-adherent Mepilex foam and wrapped with Kerlix. After 1 month of treatment, the ulcers began to reduce their dimensions. There was pink granulation tissue in the base and occasional adherent yellow fibrinous material, which was easy to remove during the wound care, without areas of necrosis (figure 2). The topical collagenase was used during admission to monitor the progression of the wound but was discontinued as outpatient treatment. Medihoney gel was applied, covered with Mepilex and wrapped with Kerlix.

Figure 2

Right lower extremity ulcer after 1 month of treatment.

Outcome and follow-up

During a period of 8 months, the patient was readmitted 29 times. In 26 admissions with pulmonary oedema and hyperkalaemia, the patient required emergent haemodialysis and was subsequently discharged. In the three other admissions, the patient was diagnosed with bacteraemia. In the first admission with bacteraemia, he also experienced erythema, oedema and pain in the wound. He was diagnosed with a dialysis catheter-related Klebsiella pneumoniae bacteraemia and a Pseudomonas aeruginosa wound infection. The haemodialysis catheter was exchanged, and he was treated with meropenem. During this admission, topical mupirocin was added to wound care. In the other two readmissions with infections, the patient had methicillin-susceptible Staphylococcus aureus and Klebsiella pneumoniae bacteraemia. He was treated with cefazolin and meropenem, respectively, as well as catheter exchange.

The wounds completely healed after 4 months of treatment (figure 3). The patient remained with normal calcium levels during all admissions and after the wounds healed.

Figure 3

Right lower extremity wounds completely healed after 4 months of treatment.


CUA is a rare condition with a mortality rate of up to 80% in a short period of time after the initial presentation, and most patients die from wound superinfections or sepsis.6 8 Although the aetiology remains unclear, most patients have abnormalities in the calcium–phosphate axis, and hypercalcaemia has been noted as a risk factor in these patients.2 9 10 In previously described patients with lower extremity CUA, the wounds healed after more than 6 months of treatment.7 9 Surgical debridement and hyperbaric oxygen therapy have been mentioned previously in the treatment of skin calciphylaxis.2 7 11 12 Our case is remarkably interesting because the patient is a man, with normal calcium levels and record wound healing after 4 months of local wound care treatment.

The patient has had multiple readmissions related to haemodialysis complications, although three admissions were related to infection. He was treated with antibiotics and wound care without complications. He is still alive 8 months after the diagnosis of calciphylaxis. Physicians should always consider CUA as a differential diagnosis of non-healing ulcers in a patient with end-stage renal disease on Coumadin.

Learning points

  • Calcific uraemic arteriolopathy (CUA) should be considered as a differential diagnosis in patients with end-stage renal disease on concurrent Coumadin and non-healing ulcers on the lower extremities.

  • CUA has a poor prognosis, a high mortality rate and is associated with frequent infections.

  • Early diagnosis, aggressive treatment with sodium thiosulfate and adequate dialysis are crucial in reducing the morbidity and mortality in patients with calciphylaxis.

  • Wound care goals should include removal of exudate and necrotic tissue to prevent infection and accelerate the wound healing process.



  • Contributors JS and DC designed the case and have been involved in the clinical management of the patient. JS and HS obtained and edited the picture. JS, DC, AY and HS have been involved in the drafting and discussion of the article. AY participated in editing the final version.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Obtained.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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