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HomeHealth articleswarfarinWhat Is Coumadin-Induced Skin Necrosis?

Coumadin-Induced Skin Necrosis - Causes, Symptoms, Diagnosis, Treatment, and Prevention

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Coumadin-induced skin necrosis is an unusual complication in patients under anticoagulant therapy and is associated with high morbidity and mortality.

Medically reviewed by

Dr. Sandhya Narayanan Kutty

Published At November 25, 2022
Reviewed AtFebruary 8, 2024


Coumadin is an oral blood-thinning medication used to manage deep vein thrombosis, pulmonary thromboembolism, cardiac bypass graft prophylaxis, and prosthetic heart valve patients. Skin necrosis from coumadin is a severe but rare condition, occurring in 1:10,000 patients who receive anticoagulant therapy, with a male-female ratio of 4:1. It has a high morbidity rate, and immediate surgical intervention with local debridement is required. Failure of early diagnosis and treatment can lead to death.

What Is Blood Coagulation?

Coagulation is a physiologic process of blood clot formation. The first stage involves primary hemostasis characterized by constriction of the blood vessel and platelet clumping at the injury site. Next, clotting involves the interaction of several blood components known as coagulation factors. Activation of factor X plays a vital role in both pathways resulting in clot formation.

The extrinsic pathway is first activated in response to a protein known as tissue factor. For example, when a blood vessel ruptures, the cells come into contact with blood containing tissue factor activating factor VII, forming factor VIIa. This activation triggers a flow of reactions resulting in the production of factor X.

An injury within a blood vessel activates the intrinsic pathway. This activates factor XII (Hageman factor), which occurs in circulating blood over the injured site. The extrinsic pathway also activates intrinsic pathway components. Cross-activation thus serves to intensify coagulation.

The production of factor X results in the division of prothrombin to thrombin. Thrombin catalyzes the conversion of fibrinogen (a soluble plasma protein) into long, sticky threads of insoluble fibrin. The fibrin threads create a mesh of platelets, blood cells, and plasma. In a few minutes, the fibrin meshwork contracts, squeezing out its fluids. This process of clot retraction is the final step in coagulation. It yields a resilient, insoluble clot that can withstand the friction of blood flow.

Coumadin is an anticoagulant that disrupts this coagulation process and maintains the blood in a fluid state.

What Are the Causes of Coumadin-Induced Skin Necrosis?

Coumadin is a commonly used blood thinner. It works by deactivating vitamin K-dependent blood clotting factors II, VII, IX, and X and Vitamin K-dependent proteins C and S, which are natural anticoagulants.

The half-life of activated protein C is less than 6 hours. So, protein C exhausts during the first few days of warfarin therapy. The half-life of factors X and II is 2-5 days, which disappears between 7 to 10 days. Sometimes, this causes excessive clotting of blood.

Thrombosis, hypersensitivity, hemorrhage, factor VII deficiency, protein C deficiency, and direct toxic effects of warfarin can potentiate skin necrosis.

The reason behind skin necrosis in the fat abundance area is unclear but can be due to decreased blood supply.

Coumadin-induced calciphylaxis may occur due to matrix protein inhibition, which is responsible for preventing calcium deposition in the blood vessels.

What Are the Risk Factors of Coumadin-Induced Skin Necrosis?

Risk factors for coumadin-induced skin necrosis include,

  • Obesity.

  • Perimenopausal age.

  • Viral infections, hepatic disease, and drug interactions.

  • Deficiency of protein S or Factor V Leiden, protein C, antithrombin III, hyperhomocysteinemia, and antiphospholipid antibodies are common underlying risk factors.

  • Large loading doses of warfarin or without an initial parallel dose of heparin.

  • Methylenetetrahydrofolate reductase gene mutation causes hyperhomocysteinemia.

What Are the Clinical Features of Coumadin-Induced Skin Necrosis?

It usually starts one to ten days after warfarin intake as sudden, localized pain and well-defined erythematous bullae formation. Next, a purplish bruise-like rash turns into bluish-black with a red rim over time. Blood sores and full-thickness skin necrosis follows. Finally, a red net-like rash may be around the dead skin area known as retiform purpura. It may be associated with paresthesia or a pressure sensation. Commonly affected areas are breasts, hips, abdomen, thighs, and buttocks. The early stage of coumadin-induced skin necrosis can cause blue toe syndrome.

What Are the Investigations for Coumadin-Induced Skin Necrosis?

Coumadin-induced skin necrosis is usually diagnosed with its clinical presentation.

Other investigations include:

  • Skin biopsy reveals clotting within blood vessels of the skin. Coumadin also precipitates calciphylaxis – a deposition of calcium in the skin.

  • Blood tests detect protein C and protein S levels in the blood.

How Is Coumadin-Induced Skin Necrosis Treated?

  • The primary treatment of coumadin-induced skin necrosis is to stop coumadin. Alternatively, heparin can be used.

  • When Coumadin therapy is stopped, small areas of skin necrosis heal, while the more significant areas require surgical intervention and skin grafting.

  • Local treatment includes topical bactericidal agents.

  • Mastectomy or amputation may be required.

  • Vitamin K or Fresh frozen plasma is used to reverse the coumadin effects. In life-threatening cases, protein C concentrates are infused.

  • Coumadin should be carefully restarted with low doses when required under the guidance of a hematologist.

How Can It Be Prevented?

  • Recognize the high-risk individuals for Coumadin therapy.

  • Start with a daily minimum dose of Coumadin instead of the loading dose.

  • Simultaneous heparin therapy can reduce thrombus progression and skin necrosis.

  • Address localized skin discomfort of the patient.

What Is the Lesion Similar to Coumadin-Induced Skin Necrosis?

Clinically, Coumadin-induced skin necrosis can mimic.

  • Calciphylaxis.

  • Microembolization (septic emboli, cholesterol emboli).

  • Thrombocytopenia and thrombosis syndrome.

  • Disseminated intravenous coagulation.

  • Purpura fulminans.

  • Necrotizing fasciitis.

  • Cryoglobulinemia (types II and III).

  • Inflammatory breast cancer.

  • Decubitus ulcers.

  • Snake venoms induced skin necrosis.


Coumadin-induced skin necrosis is an uncommon complication of anticoagulant therapy with a high morbidity and mortality rate, indicating immediate drug termination and replacement with another anticoagulant drug. When two or more drugs are simultaneously administered, laboratory investigation may help decide the causative agent. A skin biopsy, in combination with the clinical history, helps in proper diagnosis and treatment.

Frequently Asked Questions


What Does The Beginning Of Skin Necrosis Look Like?

The beginning of necrosis of the skin includes a warm, red, swollen area of the skin that spreads quickly. Severe pain includes pain beyond the area of skin that is red, swollen, and warm, and also fever can occur.


What Can Thin the Blood Quickly?

Blood thinners can thin blood quickly. Anticoagulants like Warfarin and Heparin also called coumadin slows down the body’s process of making clots. Aspirin and Clopidogrel are antiplatelets that prevent blood cells called platelets from forming a clot.


What Are The Four Steps Of Coagulation?

The four steps of coagulation are, constriction of the blood vessel, activation of the coagulation cascade, formation of a temporary “platelet plug,” and formation of “fibrin plug” or the final clot.


What Are The Factors Of Blood Coagulation?

The clotting factors are fibrinogen, prothrombin, tissue thromboplastin or tissue factor, ionized calcium, labile factor or proaccelerin, stable factor or proconvertin, and antihemophilic factor.


What Is Normal Coagulation Of Blood?

The average range for normal coagulation of blood to clot is around ten to 13 seconds. A number higher than this range means blood takes longer than usual to clot. A number lower than this range means blood clots more quickly than normal.


How Does Warfarin Cause Skin Necrosis?

The pathophysiology is not understood. Skin necrosis is a complication that is due to the initial procoagulant state that Warfarin causes, which leads to the formation of fibrin clots within the microvasculature. This blood leads to an interruption of blood supply to the skin, resulting in necrosis.


What Can Trigger Necrosis?

Necrosis can lead to injuries, diseases, and infection. Lack of blood flow in the tissues and extreme environmental conditions can cause necrosis. While the dead tissue is removed, it can be brought back to good health.


How Soon Does Skin Necrosis Spread?

Skin necrosis can spread faster. This can lead to infection and cause patches of tissue to die. These infections are due to bacteria invading tissue or skin. If not treated at the right time, it can cause death within hours.


What Are The Initial Signs Of Skin Necrosis?

Skin redness, pain, warmth, or swelling at the wound are the first signs. Skin blisters with a crackling sensation under the skin can occur. Painful skin is also a sign of severe infection, along with fever and chills.


Can Coumadin Cause Skin Problems?

Coumadin can lead to complications within a few days of administration. Immediate care is required in case of sores, color changes, temperature, or severe pain in the skin.


Are There Any Oral Blood Thinners?

Dabigatran is a thrombin inhibitor similar to the IV thrombin inhibitors earlier. Medications like Edoxaban, Apixaban, and Betrixaban are all oral blood thinners.


What Pills Can Thin Your Blood?

Anticoagulants like Warfarin and Heparin can thin the blood and slow the body's process of making clots. Antiplatelets like Clopidogrel and Aspirin can prevent blood cells called platelets from forming clots.


How Long Does It Take For Oral Blood Thinners To Work?

Blood thinners can start affecting within two to three hours. There is no need for initial injections of blood thinner, after stopping the administration, Warfarin takes around five to seven days to clear the body.


How To Recover From Skin Necrosis?

 Skin necrosis leads to necrotized tissue leading to dead devitalized tissue. This tissue cannot be rescued back and must be removed and this will lead to healing.
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Dr. Sandhya Narayanan Kutty
Dr. Sandhya Narayanan Kutty



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