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| DRUG WATCH |
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| Year : 2023 | Volume
: 55
| Issue : 5 | Page : 332-334 |
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Extensive arm skin necrosis following administration of unfractionated heparin
Dena Firouzabadi1, Peyman Petramfar2, Laleh Mahmoudi3
1 Department of Clinical Pharmacy, School of Pharmacy; Department of Clinical Pharmacy, Shahid Faghihi Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
2 Department of Neurology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
3 Department of Clinical Pharmacy, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
| Date of Submission | 21-May-2023 |
| Date of Decision | 11-Jul-2023 |
| Date of Acceptance | 29-Aug-2023 |
| Date of Web Publication | 02-Nov-2023 |
Correspondence Address:
Laleh Mahmoudi
Department of Clinical Pharmacy, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz
Iran
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/ijp.ijp_311_23
Unfractionated heparin (UH), a commonly used anticoagulant, can rarely cause skin necrosis following heparin-induced thrombocytopenia (HIT). A 38-year-old female, a case of chronic inflammatory demyelinating polyneuropathy (CIDP) admitted to the neurology ward, developed extensive skin necrosis following a change in UH dose at the exact site of UH injection. A sudden fall in the platelet count was observed within 48 h of increasing the UH dose. Necrosis of the outer layer of the skin along with clot formation and inflammation in the inner layers was detected after histopathological evaluation. UH was discontinued, and rivaroxaban was started for the patient as soon as the complication was detected. The patient was discharged in good condition after completing treatment for CIDP without any need for surgical removal of the necrotic tissue. Extensive skin necrosis, as a result of HIT, requires immediate discontinuation of UH and substitution of a nonheparin-based anticoagulation treatment.
Keywords: Heparin-induced thrombocytopenia, necrosis, unfractionated heparin
How to cite this article:
Firouzabadi D, Petramfar P, Mahmoudi L. Extensive arm skin necrosis following administration of unfractionated heparin. Indian J Pharmacol 2023;55:332-4 |
How to cite this URL:
Firouzabadi D, Petramfar P, Mahmoudi L. Extensive arm skin necrosis following administration of unfractionated heparin. Indian J Pharmacol [serial online] 2023 [cited 2023 Nov 28];55:332-4. Available from: https://www.ijp-online.com/text.asp?2023/55/5/332/389234 |
| » Introduction | |  |
Thrombocytopenia following heparin administration can paradoxically cause hypercoagulability.[1] Skin necrosis is a rare complication of clot formation after heparin-induced thrombocytopenia (HIT), with an occurrence rate of <0.2%.[2] This article reports an uncommon complication of unfractionated heparin (UH) presented as extensive arm skin necrosis. It must be mentioned that warfarin-induced skin necrosis following HIT has been reported many times in the literature; however, skin necrosis following UH use after HIT is not common. After a literature search, we found one report, presenting six cases of skin necrosis after UH use that was published in 1979, and a cohort study indicating four cases of inflammatory skin lesions, of which necrosis was confirmed in only one case.[2],[3] Two more recent reports have also been published indicating the same complication, but neither has been as massive as the presented case.[4],[5]
| » Case Report | | |
In October 2022, a 38-year-old white female, a known case of chronic inflammatory demyelinating polyneuropathy (CIDP), was admitted to the neurology ward with the chief complaint of lower-extremity weakness and paralysis. On admission, routine laboratory testing showed a normal white blood cell count (6.9 × 103/μL), a hemoglobin level of 9.7 g/dL indicating anemia, a high platelet count (521 × 103/μl), normal blood urea nitrogen and serum creatinine level (20 and 1.1 mg/dl, respectively), and a normal partial thromboplastin time (PTT) of 32 s. The initial high platelet count may be attributed to the patient's immune-mediated neuropathy. The patient's medication history included valsartan 40 mg twice daily, prednisolone 50 mg every other day, spironolactone 25 mg once daily, and famotidine 40 mg once daily. On admission, plasma exchange was planned for her treatment. Due to the immobility of the patient and to prevent deep-vein thrombosis, UH was started with subcutaneous administration of 5000 units every 12 h. Plasma exchange required the administration of a double-lumen central venous catheter. After catheterization, right cephalic venous thrombosis was detected in Doppler ultrasonography. Following this finding, the prophylactic dose of UH was changed to a therapeutic dose (80 units/kg intravenous [IV] bolus, followed by 18 units/kg/h infusion). On the same day, progressive, inflamed, and tender lesions appeared at the previous site of UH administration. These lesions further developed into an extensive site of skin necrosis on the arm and elbow within 48 h, with an obvious separation line between the necrotic tissue and its surrounding. The largest diameter of the lesion was 10 cm × 4.5 cm [Figure 1]. The patient had a prolonged PTT of 20.4 s on the day of the start of the reaction. However, platelet fall occurred with delay, 2 days after the reaction, and declined to 61 × 103/μL. Necrosis of the outer layer of the skin along with clot formation and inflammation in the inner layers was detected after histopathological evaluation. Enzyme-linked immunosorbent assay revealed negative results for the heparin–platelet factor-4 antibody. Protein C and protein S were also within the normal range. | Figure 1: Skin necrosis in a 38-year-old white female due to heparin-induced thrombocytopenia
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UH treatment was discontinued after the detection of this complication. Rivaroxaban 15 mg two times a day was started. The patient was discharged in good condition after completing treatment for CIDP, without the need for surgical debridement of the site of the necrosis.
| » Discussion | | |
Heparin-induced skin necrosis is a very rare complication of UH administration, estimated to occur in only 10%–20% of HIT cases. It is expected to occur between days 5 and 11 after the initiation of therapy; however, earlier reactions (3–7 days) have been reported in patients with a previous history of heparin consumption. Antibody formation has been reported to be higher in surgical patients compared to nonsurgical medical patients. As for our case, the lesions started 8 days following prophylactic consumption of UH and promptly after the initiation of IV UH infusion. The probability of necrosis following HIT has been attributed to the extent of the decrease in platelet count, and higher rates of decline from baseline have been associated with a higher likelihood of thrombosis following HIT. The formation of tender, erythematous, and inflamed lesions at the site of injection may be its first presentation that further transforms into bolus lesions with evident necrosis. In this condition, diagnosis is usually based on clinical findings, although a biopsy can be helpful. To control the complication, it is necessary to stop the heparin infusion as soon as possible, and if a large area of necrotic tissue is formed, surgical procedures may be needed to remove the necrotic tissue along with the requirement for skin grafting. In our case, the platelet count fall took place 48 h after the eruption of skin lesions. According to previous reports, heparin-induced skin lesions could be attributed to antibody-mediated HIT and may appear in the absence of or before conventionally described thrombocytopenia. These lesions manifest as a delayed-type hypersensitivity reaction that can further develop into necrotic cutaneous tissue, usually exhibiting a central black eschar surrounded by erythema as observed in our case and shown in [Figure 1]. In the presented case, microvasculature thrombosis was confirmed after histopathologic evaluation of the necrotic tissue. Following suspicion of HIT, all sources of heparin must be discontinued, and alternative anticoagulants must be started.
In very severe cases of skin necrosis and skin loss following heparin use, complications may arise, and also, due to the possible propagation of clot formation following the continuation of UH, fatality may be expected if immediate action toward a diagnosis of probable HIT is not taken. However, our case was managed properly by replacing a nonheparin anticoagulant (rivaroxaban) once HIT was suspected, and wound care was further applied for the patient using a hydrogel wound dressing along with prophylactic empiric administration of cefazolin 1 g q8h for 3 days until wound erythema resolved; crust formation was evident while the patient was hemodynamically stable. The patient was discharged in good condition after completion of CIDP management without the need for surgical removal of the necrotic tissue.
| » Conclusion | | |
Heparin-induced skin necrosis following UH use is an uncommon complication requiring prompt recognition and replacement of treatment with a nonheparin anticoagulant to prevent life-threatening complications.
Ethics approval code
This case report study has been reviewed and approved by the Ethics Committee Board of Shiraz University of Medical Sciences and has been allocated a unique code: IR.SUMS.REC.1401.703.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published, and due efforts will be made to conceal her identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| » References | | |
| 1. | Baroletti SA, Goldhaber SZ. Heparin-induced thrombocytopenia. Circulation 2006;114:e355-6.  |
| 2. | Warkentin TE, Roberts RS, Hirsh J, Kelton JG. Heparin-induced skin lesions and other unusual sequelae of the heparin-induced thrombocytopenia syndrome: A nested cohort study. Chest 2005;127:1857-61. |
| 3. | White PW, Sadd JR, Nensel RE. Thrombotic complications of heparin therapy: Including six cases of heparin-induced skin necrosis. Ann Surg 1979;190:595-608. |
| 4. | Pasha AK, McBane Ii RD. Heparin skin necrosis in heparin-induced thrombocytopenia. Mayo Clin Proc 2021;96:2492. |
| 5. | Chidharla A, Rapoport EA, Naffakh N, Roberts JC. A challenging case of heparin-induced skin necrosis without thrombocytopenia. Blood Coagul Fibrinolysis 2022;33:134-7. |
[Figure 1]
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