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Delayed Onset Low Molecular Weight Heparin Induced Skin Necrosis in a Hemodialysis Patient

Suzanne  J. Sanchez , M.D.,  Ruben A.  Maguad , M.D.,  Grecia  P.  Darunday , M.D. The Kidney Service  Perpetual  Succour   Hospiral Cebu City, Philippines

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19TH ASIAN PACIFIC CONGRESS OV NEPHROLOGY
2021 THAILAN
19 - 22 AUGUST 2021

Low molecular weight heparin (LMWH)  U sed as prophylaxis for venous thromboembolic diseases Treatment  Deep vein thrombosis P ulmonary embolism A cute myocardial infarction Anticoagulant of choice during hemodialysis

Humphries, J. E., Kaplan, D. M., & Bolton, W. K. (1991). Heparin Skin Necrosis: Delayed Occurrence in a Patient on Hemodialysis.  American Journal of Kidney Diseases ,  17 (2), 233–236.  doi : 10.1016/s0272-6386(12)81135-8 Katsourakis , A.,  Noussios , G.,  Kapoutsis , G., &  Chatzitheoklitos , E. (2011). Low Molecular Weight Heparin-Induced Skin Necrosis: A Case Report.  Case Reports in Medicine ,  2011 , 1–2.  doi : 10.1155/2011/857391

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Heparin Induced Skin Necrosis Usually occurs at the site of subcutaneous injection Typically develops within 2 weeks of starting therapy

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There are very few reports on heparin induced skin necrosis occurring in hemodialysis patients Although rare, recognition is vital as continued use will risk patients to develop life  threatening complications

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62 year old Female AKI  secondary to Obstructive Nephropathy secondary to Right  Ureterolithiases  s/p DJ stent placement, right (March 2019) on top of CKD secondary to DM nephropathy s/p IJ catheter insertion (March 2019) on HD 2x a week Enoxaparin  0.2cc IV as HD anticoagulant.

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On her regular HD session (3 months after initiation of HD), patient noted with chills at 1 st  hour of HD Blood  CS was requested which showed growth of  Klebsiella   pneumoniae Started  on  vancomycin  500mg IV infusion for 1h after negative skin test 2 days after, she sought consult due to right leg pain

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She was admitted as a case of Cellulitis right leg and left hand IV  antibiotic was started. Maintenance medications were  continued Intact  PTH was normal

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HD  was continued 2x a week with enoxaparin as  anticoagulant It was then noted that inflammation on both right leg and left hand flares during and after  HD

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Prednisone 20mg/tab 1 tab BID was started Vancomycin   and enoxaparin  were  discontinued HD  continued 3x a week with no anticoagulant There  was noted  lysis  of fever and decrease inflammation of the right leg and left forearm

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HD  then continued 3x a week without anticoagulant Progressive  improvement of induration of both arms. No recurrence of inflammation of the right leg. Debridement  of necrotic tissue  was done Biopsy  of the left forearm induration showed superficial perivascular dermatitis  without thrombosis or calcifications, while the right leg induration showed dermal necrosis with focal epidermal ulceration without thrombosis or calcifications

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Heparin induced skin necrosis is a rare adverse effect. It usually affects middle aged and obese women. The skin necrosis usually appears between day 5 to 15  from initiation of therapy.

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Late onset heparin induced skin necrosis was reported in this case, as long as 3 months after the initiation of therapy in a hemodialysis patient – this may be due to to the intermittent administration of heparin during dialysis Skin necrosis starts with erythema, edema, and severe pain, which eventually evolved into a bullae, and then  necrosed

Handschin , A. E.,  Trentz , O.,  Kock , H. J., &  Wanner , G. A. (2004). Low molecular weight heparin-induced skin necrosis—a systematic review.  Langenbecks  Archives of Surgery ,  390 (3), 249–254.  doi : 10.1007/s00423-004-0522-7 Godet , T.,  Perbet , S.,  Lebreton , A.,  Gayraud , G.,  Cayot , S., Tremblay, A.  Constantin , J.-M. (2013). Low Molecular Weight Heparin Induced Skin Necrosis without Platelet Fall Revealing  Immunoallergic  Heparin Induced Thrombocytopenia.  Case Reports in Hematology ,  2013 , 1–3.  doi : 10.1155/2013/ 849168

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In most cases, it usually occurs locally at the injection site. Distant distribution may be seen especially in patients given IV heparin as what was seen in our patient

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Skin necrosis commonly occurs at sites with abundant adipose tissue, such as the abdomen and thighs. This is postulated to be due to the fat tissue’s poor blood circulation. In our case, it occurred in the right foot and bilateral forearms, which were sites not very rich in adipose tissue

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Diagnosis of heparin induced skin necrosis in this case was done  clinically  and  by exclusion Due to the fact that patient was given multiple IV antibiotics, initially these were regarded as the culprit for the hypersensitivity reaction Also since patient is a known case of Chronic Kidney Disease,  calciphylaxis  was likewise entertained. But  iPTH  and biopsy did not prove otherwise. It was noted that with discontinuation of use of the low molecular weight  heparin, there was resolution of the skin necrosis

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Delayed onset low molecular weight heparin induced skin necrosis is a serious adverse effect if not diagnosed early. The most important aspect in the management of this condition is early recognition and discontinuation of use.

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With regards to patients on hemodialysis who require long term use of heparin as anticoagulant, management is difficult. As in our case, alternative anticoagulant such as  fondaparinaux  also resulted in flaring of the skin necrosis.

Delayed Onset Low Molecular Weight Heparin Induced Skin Necrosis in a Hemodialysis Patient

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