Ans: Purpura fulminans / Warfarin induced skin necrosis.
Explanation: Purpura Fulminans is an acute syndrome of massive purpura caused by widespread vascular necrosis and hemorrhagic infarction of the skin and frequently of the distal limbs and digits. It may occur at birth as a result of congenital thrombophilia (i.e. homozygous deficiency of protein C or protein S), durin DIC, with severe infections such as meningococcemia, or after the administration of warfarin(i.e. warfarin skin necrosis). Rare causes are chronic alcohol abuse, acetaminophen ingestion, antiphospholipid antibodies with or without transient acquired protein S deficiency after varicella infection. The skin necrosis observed with heparin is another thrombotic manifestation of the heparin-dependent platelet autoantibody syndrome, caused by antibodies against heparin complexed with platelet factor-4.
The early clinical appearance of Purpura Fulminans is transient flushing, followed by petechiae, with or without edema. At presentation, however, the appearance is usually of massive raised and indurated bruises. The periphery of the lesions may be hyperemic; the center may be replaced by hemorrhagic bullae and necrosis of the skin, with sparing of the subjacent musclle. Dependent areas are typically involved, but the predilection for the breasts, fatty tissue (i.e. abdominal wall and buttocks), and penis is not understood. Areas of pressure may be involved.
The histopathological findings are thrombosis of the dermal capillaries and venules, with hemorrhagic infarction. Arteries and arterioles are spared. The thrombi are composed of fibrin, platelets, or a mixture of the two. There are few or no associated inflammatory changes.
There is a general agreement that Purpura Fulminans results from an imbalance of pprocoagulants and the vitamin K-dependent anticoagulant protein C and S.
Numerous cases of skin necrosis have been observed after warfarin administration, especially when a large loading dose has been used. Warfarin-induced necrosis is more common in women. It has a prevalence between 0.01 and 0.1 percent and typically presents 3 to 10 days after treatment initiation. Late-onset warfarin necrosis has been reported in a patient who developed palpable purpura with rapid progression to hemorrhagic bullae on her abdomen and thighs 56 days after initiation of warfarin treatment for heart valve replacement.
The incidence is highest during the first 3 days of drug administration because protein C has a short half life (6 to 9 hrs) compared with the other vitamin K-dependent procoagulant factors IX, X and II. Twenty four hrs after initiation of warfarin, the level of protein C may be less than 10% of normal, whereas functional levels of procoagulant vitamin-K dependent factors (other than factor VII) may be still greater than 50%. The problem is accentuated in individuals who are heterozygous for protein C deficiency, which may account for as muchas 2% of the population. Warfarin induced skin necrosis has been reported occasionally in patients who are protein S deficient. In individuals with normal protein c and S levels, anti-phospholipid antibodies may stimulate a deficiency state by interfering with endothelial-dependent protein C activation by thrombomodulin.
Treatment involves prompt cessation of warfarin therapy and occasionally surgical intervention if gangrenous tissue develops. Methicillin-resistant Staphylococcus aureus infection of widely involved areas of warfarin necrosis can lead to fatal septic shock. If protein C or S def is suspected, it is common practice to begin cautious warfarin therapy while the patient is heparinized. However, anecdotal evidence of skin necrosis, even in this setting, has been reported. The most important method of prevention is the use of low initial dose of warfarin. A loading dose has no physiological advantage and is no longer recommended.
Ref: 1. Thrombosis and hemorrhage by Joseph Loscalzo, Andrew I. Schafer, 3rd edition 2. Williams Hematology, 7th edition
Thanx for all this info...nice post...
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