Warfarininduced venous limb ischemiagangrene complicating. Pdf venous limb gangrene during overlapping therapy with. Warfarininduced skin necrosis and venous limb gangrene in the. Warfarininduced venous limb gangrene and skin necrosis are both a reflection of a relatively hypercoagulable state created by initiation of warfarin therapy. Venous limb gangrene during overlapping therapy with. Warfarininduced venous limb gangrene following heparin. Warfarin is widely used for the prevention of cerebral infarction, especially in patients with atrial fibrillation or artificial valve. Arterial thrombosis lower limb arterial thrombosis 20% require amputation cva myocardial infarction 35% other arterial thrombosis including mesenteric, brachial and spinal 3. The wacky hypercoagulable state of malignancy blood. We report a case of skin necrosis induced by warfarin therapy. Warfarin therapy in patients with hit can cause progression of deep venous thrombosis to venous limb gangrene. Although warfarin is most notoriously associated with skin necrosis, the occurrence of venous limb gangrene has been reported previously both in patients with heparininduced thrombocytopenia hit and in patients with malignancy.
We seek to confirm and increase awareness of the risks of warfarin with hit. A case of venous gangrene, treated successfully with. Warfarininduced gangrene may present as the classic picture of coumarin skin necrosis with involvement of the dermal and subdermal tissues predominantly at central nonacral sites such as the breast, abdomen. Venous limb gangrene during warfarin treatment of cancerassociated deep venous thrombosis. Heparininduced thrombocytopenia hit is a common, often catastrophic, syndrome that produces the most hypercoagulable of states, with 30% to 75% of patients having thrombotic complications. Warfarininduced skin necrosis and venous limb gangrene in the setting of heparininduced thrombocytopenia article pdf available in archives of internal medicine 1641. Warfarininduced penile necrosis in a patient with heparininduced. Warfarin natural anticoagulant depletion during warfarin therapy induced skin necrosis and venous limb gangrene with heparin induced of hitassociated hypercoagulability 16. Venous gangrene is rare condition which is associated with poor prognosis in cancer patients. Twelve days after starting heparin, an aboveknee amputation was required for warfarininduced venous limb gangrene. Venous gangrene complicating deep vein thrombosis dvt in the context of anticoagulation use in patients with gynecological malignancy is rarely reported. Although hemorrhagic problems are well known, skin necrosis is a rare complication. Warfarininduced penile necrosis in a patient with heparin.
Warfarininduced skin necrosis venous limb gangrene 16 protein halflife procoagulanteffects vii 46 hrs ix 2 hrs x 2748 hrs ii 4172 hrs anticoagulanteffects. Warfarin associated venous limb gangrene in cancerrelated dvt. Venous dvt lower limb upper limb cvc pe adrenal vein hemorrh. Heparininduced thrombocytopenia and warfarininduced skin.
Warfarininduced skin necrosis and venous limb gangrene in. Both cutaneous adverse effects share the same pathophysiology. During anticoagulation therapy with heparin, attention must be paid to the risk of critical hit. Warfarininduced skin necrosis is a rare complication of anticoagulant therapy with a high associated morbidity and mortality requiring immediate drug cessation. Venous limb gangrene vlg the link between hit and venous thrombosis is underscored by venous limb gangrene vlg. Malignancyassociated venous thrombosis with concurrent warfarininduced skin necrosis, venous limb gangrene and thrombotic microangiopathy. Warfarininduced penile necrosis in a patient with heparininduced thrombocytopenia. However, when hit complicates thromboprophylaxis, the amount of heparin is too low to prevent hypercoagulability, enhancing venous thrombotic risk. An 84yearold woman with warfarininduced venous limb gangrene presenting with ischemic skin necrosis on the distal ends of her amputation sites. The diagnosis can be delayed if not suspected due to its rare occurrence and invariably result in a fatal outcome. Limb gangrene in cancer patients receiving warfarin.
The majority of cases of warfarininduced venous limb gangrene has been in patients with cancer or heparininduced thrombocytopenia. In both patients, therapy with the direct thrombin inhibitor was interrupted during persisting severe. Warfarin treatment of deep venous throm bosis associated with heparininduced thrombocytopenia is a possible cause of venous limb gangrene. Venous thrombosis dvt 50% warfarininduced venous limb gangrene pe 25% cerebral venous thrombosis adrenal infarction 2. Failures of early diagnosis or management may lead to serious results. However, in patients with warfarininduced venous limb gangrene, warfarin does not adequately prevent thrombinantithrombin complex formation. Pdf warfarin induced skin necrosis semantic scholar. Both cutaneous adverse effects share the same pathophysiology, but are clinically quite different. This case report documents a 53yearold woman who developed bilateral lower limb dvt while being on a. Furthermore, the risk of warfarin causing venous limb. Heparininduced thrombocytopenia and warfarininduced skin necrosis. She continued to receive warfarin and still improved, with inr being maintained between 23.
Warfarininduced venous limb gangrene mayo clinic proceedings. The patients without any diagnosis of neoplasia, undergoing the progression from dvt to warfarininduced. Hit, for example, warfarininduced venous limb gangrene11 and skin necrosis12 syndromes. We describe 6 patients with hit seen at 3 medical centers in whom frank or impending venous limb gangrene, central skin necrosis, or both were temporally related to warfarin initiation. Furthermore, there is evidence to suggest that warfarininduced venous limb gangrene. Ovarian malignancy unmasked by venous gangrene in a. The patients without any diagnosis of neoplasia, undergoing the progression from dvt to warfarininduced venous limb gangrene, should be investigated for cancer. If the address matches an existing account you will receive an email with instructions to reset your password. Venous limb gangrene during overlapping therapy with warfarin and a direct thrombin inhibitor for immune heparininduced thrombocytopenia. It is recommended that warfarin not be started until substantial resolution of thrombocytopenia has occurred preferably. Warfarin associated venous limb gangrene in cancerrelated. An alternative diagnosis of venous limb gangrene was excluded. Warfarin is a very commonly used anticoagulant in medical practice.
The punch biopsies were consistent with wisn, and the patient did not have a deep venous thrombosis or distal ischemic necrosis of the limbs consistent with venous limb gangrene. Heparininduced thrombocytopenia complicated by warfarin. Ovarian malignancy unmasked by venous gangrene in a patient on. We report two patients with deepvein thrombosis complicating immune heparininduced thrombocytopenia who developed venous limb gangrene during overlapping therapy with a direct thrombin inhibitor lepirudin or argatroban and warfarin. Srinivasan and others published warfarininduced skin necrosis and venous limb gangrene in the setting of heparininduced thrombocytopenia find, read and cite. Venous thromboembolism is often encountered in cancer patients and is usually treated with heparin followed by warfarin. Warfarininduced skin necrosis wisn is a rare but catastrophic complication of warfarin therapy, ranging in prevalence from 0. A young womans warfarin associated acute ileofemoral phlegmasia that developed over cervical cancer radiation therapy induced dvt, was successfully. Warfarininduced venous limb gangrene is a distinct entity from warfarininduced skin necrosis. Formation of procoagulant, plateletderived microparticles, and, possibly, activation of endothelium generate thrombin in vivo. This led the admitting physician to incorrectly label the patient as allergic to warfarin. The pathogenesis of venous limb gangrene associated with heparininduced thrombocytopenia. Recent data show that up to 8% of heparinized patients will develop the antibody associated with hit and that approximately 15% of patients on heparin will progress to develop hit with thrombocytopenia 11, 12, suffering from venous andor arterial thrombosis in at.
Isth advanced course, cascais, portugal sat 15 mar 2014. Warfarininduced skin necrosis should be suspected in all patients who undergo aggressive warfarinization, even with an initially normal clotting profile. Heparininduced thrombocytopenia is the most important of the immunemediated, druginduced thrombocytopenias. In a series of hit patients with venous limb gangrene, warkentin et al. The complications associated with warfarin therapy have also been known for a long time. Thrombin generation helps to explain the strong association between hit and thrombosis, including the newly recognized syndrome of warfarininduced venous limb gangrene. There are also reports of warfarininduced skin necrosis. Warfarin treatment of deep venous thrombosis associated with heparininduced thrombocytopenia is a possible cause of venous limb gangrene, perhaps because of acquired failure of the protein c. All compartment fasciotomy may improve arterial supply in phlegmasia cerulea dolens by relieving the excessive intracompartimental pressure. A fatal thrombotic disorder associated with an acquired inhibitor of protein c. Among their studys end points, the authors did not list 2 such sequelae.
Warfarininduced venous limb ischemiagangrene complicating cancer. Warfarin is a commonly used anticoagulant that has been associated with several significant cutaneous side effects, most notably warfarininduced skin necrosis. Due to its infrequency and the fact that it presents much differently than warfarininduced skin necrosis, physicians may dismiss the fact that warfarin is the cause of a patients necrosis. Warfarin predisposes to microvascular thrombosis in patients with acute hit, for example, warfarininduced venous limb gangrene 11 and skin necrosis 12 syndromes. Warfarininduced skin necrosis typically occurs in obese, perimenopausal women of around. The author has received an honorarium as a consultant for.
The main adverse effect of warfarin therapy is bleeding, but limb ischemia and gangrene can occasionally occur, usually in association with heparininduced thrombocytopenia hit. The pathogenesis of vg is multifactorial and could paradoxically be due to warfarin. Warfarininduced skin necrosis and venous limb gangrene in the setting of heparininduced thrombocytopenia. Affected patients typically have a supratherapeutic inr typically 4. Venous limb gangrene during overlapping therapy with warfarin and.
Discussion warfarininduced skin necrosis is the result of a relatively hyper coagulable state produced by warfarin. Notealsotheulcerationson herleft knee,which developedatthesametime, likely due to less severe vascular occlusions. Two patients developed catastrophic multicentric skin necrosis while receiving warfarin to treat venous thromboembolism complicated by immune. Safety of warfarin anticoagulation in patients with. Transient global amnesia arterial limb cva mi skin necrosis at sc injection sites microvascular warfarin necrosis venous limb gangrene central skin necrosis dic without thrombosis clinical picture of hit number of cases. Persisting thrombin generation occurs despite elevated inr, indicating severe pc depletion that occurs in parallel with reduced factor vii. On the other hand, venous limb gangrene complicating warfarin. Warfarininduced skin necrosis is an infrequent complica. Patient 1 developed skin necrosis involving the breasts, thighs, and face, as well as venous limb gangrene and bilateral hemorrhagic necrosis of the adrenal glands, resulting in death. Devastating thromboses can complicate heparininduced thrombocytopenia hit and disseminated intravascular coagulation dic. In these disorders, acquired abnormalities of the partial thromboplastin time ptt and international normalized ratio inr can confound monitoring of ptt and inradjusted anticoagulant therapies, contributing to treatment failure.