warfarin and Gangrene

Recommendations for transitioning from therapy with heparin or a low-molecular-weight heparin preparation to therapy with an oral anticoagulant in patients with acute venous or arterial thromboembolism have undergone several changes during the last two decades. Physicians are now comfortable with beginning treatment with an oral anticoagulant once the diagnosis is confirmed, and loading doses are no longer considered to be necessary. Exceptions to early transition may be necessary in patients with an extensive iliofemoral or axillary-subclavian vein thrombosis or pulmonary embolism where thrombolytic agents may be indicated, or in individuals who require surgery or other invasive procedures, or if there are concerns about bleeding. The avoidance of early transition to oral anticoagulants in patients with acute heparin-induced thrombocytopenia also has been advised because of the potential for further thrombotic complications, including venous limb gangrene and warfarin-induced skin necrosis.

Topics: Administration, Oral; Anticoagulants; Arginine; Blood Coagulation; Blood Coagulation Factors; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Gangrene; Heparin; Heparitin Sulfate; Hirudins; Humans; Ischemia; Leg; Necrosis; Pipecolic Acids; Recombinant Proteins; Skin; Sulfonamides; Thrombocytopenia; Thrombosis; Warfarin

Deep-vein thrombosis (DVT) and pulmonary embolism are among the most common complications of heparin-induced thrombocytopenia (HIT), an antibody-mediated adverse effect of heparin that leads paradoxically to in vivo activation of platelets and the coagulation system. Inappropriate treatment of HIT-associated DVT with warfarin can cause the DVT to progress to limb gangrene: this results from impaired ability of the protein C natural anticoagulant pathway to down-regulate thrombin generation, thus leading to microvascular thrombosis and tissue necrosis. Appreciation of the importance of coagulation system activation in HIT provides a rationale for treatments that reduce thrombin generation, either via inhibiting factor Xa (danaparoid) or via inhibiting thrombin directly (lepirudin). Clinicians should know how to distinguish HIT from other thrombocytopenic disorders: for example, thrombocytopenia associated with pulmonary embolism can mimic HIT (pseudo-HIT), and acute dyspnea that can mimic acute pulmonary embolism can result from acute in vivo platelet activation in a patient with HIT antibodies who receives heparin bolus therapy (pseudo-pulmonary embolism).

Topics: Anticoagulants; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Gangrene; Heparin; Heparitin Sulfate; Humans; Leg; Pulmonary Embolism; Thrombocytopenia; Venous Thrombosis; Warfarin

The past decade has seen many important advances in the pathogenesis, clinical and laboratory diagnosis, and management of heparin-induced thrombocytopenia (HIT), one of the most common immune-mediated adverse drug reactions. HIT is caused by IgG antibodies that recognize complexes of heparin and platelet factor 4, leading to platelet activation via platelet Fc gamma IIa receptors. Formation of procoagulant, platelet-derived microparticles, and, possibly, activation of endothelium generate thrombin in vivo. Thrombin generation helps to explain the strong association between HIT and thrombosis, including the newly recognized syndrome of warfarin-induced venous limb gangrene. This syndrome occurs when acquired protein C deficiency during warfarin treatment of HIT and deep venous thrombosis leads to the inability to regulate thrombin generation in the microvasculature. The central role of HIT antibodies in causing HIT, as well as refinements in laboratory assays to detect these antibodies, means that HIT should be considered a clinicopathologic syndrome. The diagnosis can be made confidently when one or more typical clinical events (most frequently, thrombocytopenia with or without thrombosis) occur in a patient with detectable HIT antibodies. The central role of thrombin generation in this syndrome provides a rationale for the use of anticoagulants that reduce thrombin generation (danaparoid) or inhibit thrombin (lepirudin).

Topics: Antibodies; Anticoagulants; Antithrombin III; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Fibrinolytic Agents; Gangrene; Heparin; Heparinoids; Heparitin Sulfate; Hirudin Therapy; Hirudins; Humans; Immunoglobulin G; Leg; Platelet Activation; Platelet Factor 4; Protein C Deficiency; Receptors, IgG; Recombinant Proteins; Retrospective Studies; Syndrome; Thrombin; Thrombocytopenia; Venous Thrombosis; Warfarin

Heparin-induced thrombocytopenia (HIT) may be complicated by severe thrombotic complications and death. Currently no specific laboratory test is available to make the diagnosis. When HIT is clinically suspected, heparin should be discontinued immediately. While no specific therapy for HIT exists, there is increasing evidence that acute antithrombin therapy may significantly reduce morbidity and mortality. Among several agents, the direct antithrombins, such as r-hirudin and argatroban, look the most promising for acute treatment.

Topics: Ancrod; Arginine; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Fibrinolytic Agents; Forecasting; Gangrene; Hemorrhage; Heparin; Heparitin Sulfate; Hirudin Therapy; Hirudins; Humans; Pipecolic Acids; Platelet Aggregation; Protein C; Recombinant Proteins; Sulfonamides; Thrombin; Thrombocytopenia; Warfarin

Two patients developed catastrophic multicentric skin necrosis while receiving warfarin to treat venous thromboembolism complicated by immune-mediated heparin-induced thrombocytopenia (HIT). 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. The second patient developed bilateral mammary necrosis necessitating mastectomies, as well as skin necrosis involving the thigh. Neither patient had an identifiable hypercoagulable syndrome, other than HIT. HIT may represent a risk factor for the development of multicentric warfarin-induced skin necrosis (WISN).

Topics: Adrenal Gland Diseases; Aged; Amputation, Surgical; Anticoagulants; Antigens, Human Platelet; Autoantibodies; Autoimmune Diseases; Databases, Factual; Disseminated Intravascular Coagulation; Ecchymosis; Fatal Outcome; Female; Gangrene; Hemorrhage; Heparin; Humans; Mastectomy; Middle Aged; Multiple Organ Failure; Necrosis; Postoperative Complications; Pulmonary Embolism; Skin; Skin Diseases; Thigh; Thrombin; Thrombocytopenia; Thrombophilia; Thrombophlebitis; Vena Cava Filters; Warfarin

Until recently, the confusing clinical profile of HIT and the widespread unavailability of reliable diagnostic assays have conspired to produce under-recognition-if not frank skepticism-of the clinical importance of HIT. However, during the 1990s, HIT has emerged as one of the major-if not the most important-immunohematologic problems in clinical medicine. The clinical and laboratory investigations summarized here have contributed to a greater understanding of the frequency, clinical spectrum, pathogenesis, laboratory diagnosis, and-potentially-the prevention of this important drug allergy. Further, the demonstration of increased platelet procoagulant activity and, thrombin generation in HIT, together with insights into the pathogenesis of a new clinicopathologic syndrome (venous limb gangrene), help explain how a disorder characterized by IgG-mediated platelet activation can lead to such diverse clinical sequelae as venous thrombosis, pulmonary embolism, disseminated intravascular coagulation, and venous limb gangrene. These studies should lead to improved treatment of HIT (new emphasis on suppression of thrombin generation, eg, hirudin and its analogs), future avoidance of HIT (preparation of low-molecular-weight heparins and heparinoids that are less immunogenic), and a greater understanding of the interaction between platelet activation and procoagulant/anticoagulant processes.

Topics: Extremities; Gangrene; Heparin; Humans; Immunoglobulin G; Platelet Activation; Thrombin; Thrombocytopenia; Thrombosis; Warfarin

COVID-19 and Fontan physiology have each been associated with an elevated risk of venous thromboembolism (VTE), however little is known about the risks and potential consequences of having both.. A 51 year old male with tricuspid atresia status post Fontan and extracardiac Glenn shunt, atrial flutter, and sinus sick syndrome presented with phlegmasia cerulea dolens (PCD) of the left lower extremity in spite of supratherapeutic INR in the context of symptomatic COVID-10 pneumonia. He was treated with single session, catheter directed mechanical thrombectomy that was well-tolerated.. This report of acute PCD despite therapeutic anticoagulation with a Vitamin K antagonist, managed with emergent mechanical thrombectomy, calls to attention the importance of altered flow dynamics in COVID positive patients with Fontan circulation that may compound these independent risk factors for developing deep venous thrombosis with the potential for even higher morbidity.

Topics: Amputation, Surgical; Atrial Flutter; COVID-19; Fontan Procedure; Gangrene; Heart Defects, Congenital; Humans; Image Processing, Computer-Assisted; Lower Extremity; Male; Mechanical Thrombolysis; Middle Aged; Phlebography; Postoperative Complications; Sick Sinus Syndrome; Thrombophlebitis; Tomography, X-Ray Computed; Treatment Outcome; Tricuspid Atresia; Warfarin

Thromboangiitis obliterans (TAO) is a chronic, non-atherosclerotic, progressive inflammatory vascular disease affecting the small- and medium-size arteries and veins of the extremities.. To evaluate whether long-term anticoagulation with low-molecular-weight heparin (LMWH) and warfarin is beneficial for treating the inflammation and symptoms associated with TAO.. Patients with TAO who underwent anticoagulation as the mainstay of treatment were included in this prospective study. Rest pain relief and healing of trophic lesions (as the primary and secondary endpoint) were investigated at Day 14 and after 6 months of follow-up. High sensitivity C-reactive protein (hsCRP), monocyte count, and ankle-brachial index (ABI) were recorded, and the difference was compared before and after 2-week anticoagulation. The Chi-square test was used to compare the difference between anticoagulant and aspirin groups (based on the literature).. From 2014 to 2019, 18 patients were included. Only 1 patient with wet gangrene received endo-therapy for a failing stent at the start of treatment. After ~14 days, 12 of 13 (92%) patients showed complete ulcer healing, and 17 of 18 (94%) patients showed complete relief from rest pain. Monocyte-counts and hsCRP levels decreased significantly (p<0.001) after a 2-week period of anticoagulation with LMWH. The mean follow-up was 2.6 years (range 0.5-5 years). At 6 months, all patients showed relief of rest pain and complete healing of trophic lesions. All endpoints were significantly improved compared with the aspirin group (p<0.01), and no rest pain or ulcer/gangrene recurred during follow-up.. Anticoagulant therapy may alleviate the inflammation and symptoms of TAO.

Topics: Anticoagulants; Aspirin; C-Reactive Protein; Gangrene; Heparin, Low-Molecular-Weight; Humans; Inflammation; Pain; Prospective Studies; Thromboangiitis Obliterans; Treatment Outcome; Ulcer; Warfarin

Venous gangrene complicating deep vein thrombosis in the context of anticoagulation use in patients with gynecologic malignancy is rarely reported. We report an unusual presentation of venous gangrene of the lower limbs associated with warfarin therapy in a 53-year-old woman from the Cook Islands with an occult ovarian cancer.. A 53-year-old woman of Cook Islands origin presented with exertional dyspnea, rapid atrial fibrillation, bilateral lower limb edema, and painful digital ischemia of her hallux. She was on warfarin therapy for atrial fibrillation and had a stable therapeutic international normalized ratio. Bilateral proximal lower limb deep vein thrombosis and digital gangrene subsequently developed in the setting of a supratherapeutic international normalized ratio and platelet count depletion. Her warfarin was reversed and heparin therapy was commenced with resulting correction of her thrombocytopenia.. We would like to attract the attention of the reader to the potential hazard of the use of warfarin in patients with malignancy. In our case, we also demonstrated a predictive value of supratherapeutic international normalized ratio and platelet count depletion that could herald massive thrombosis and gangrene in a patient who was previously stable on warfarin therapy. Early recognition and prompt reversal of warfarin in these circumstances is essential to correct the unbalanced prothrombotic process that leads to extensive thrombosis and gangrene. The outlook of such cases remains dismal and results in extensive morbidity and mortality.

Topics: Anticoagulants; Atrial Fibrillation; Female; Gangrene; Heparin; Humans; International Normalized Ratio; Ischemia; Middle Aged; Obesity, Morbid; Ovarian Neoplasms; Thrombocytopenia; Toes; Ultrasonography, Doppler; Venous Thrombosis; Warfarin

Venous limb gangrene (VLG) can occur in cancer patients, but the clinical picture and pathogenesis remain uncertain. We identified 10 patients with metastatic cancer (7 pathologically proven) who developed severe venous limb ischemia (phlegmasia/VLG) after initiating treatment of deep-vein thrombosis (DVT); in 8 patients, cancer was not known or suspected at presentation. The patients exhibited a novel, clinically distinct syndrome: warfarin-associated supratherapeutic international normalized ratio (INR; median, 6.5) at onset of limb ischemia, rising platelet count during heparin anticoagulation, and platelet fall after stopping heparin. Despite supratherapeutic INRs, patient plasma contained markedly elevated thrombin-antithrombin (TAT) complex levels (indicating uncontrolled thrombin generation) and protein C (PC) depletion; this profile resembles the greatly elevated TAT/PC activity ratios reported in patients with warfarin-associated VLG complicating heparin-induced thrombocytopenia. Analyses of vitamin K-dependent factors in 6 cancer patients with available serial plasma samples showed that variations in the INR corresponded most closely with changes in factor VII, with a highly collinear relationship between VII and PC. We conclude that venous limb ischemia/gangrene is explained in some cancer patients by profoundly disturbed procoagulant-anticoagulant balance, whereby warfarin fails to block cancer-associated hypercoagulability while nonetheless contributing to severe PC depletion, manifest as a characteristic supratherapeutic INR caused by parallel severe factor VII depletion.

Topics: Aged; Anticoagulants; Antithrombin III; Blood Coagulation Factors; Blood Platelets; Female; Follow-Up Studies; Gangrene; Heparin; Humans; International Normalized Ratio; Ischemia; Leg; Male; Middle Aged; Neoplasms; Peptide Hydrolases; Prognosis; Protein C Deficiency; Syndrome; Venous Thrombosis; Vitamin K; Warfarin

In this issue of Blood, Warkentin et al describe a novel clinical syndrome of warfarin-associated severe venous limb ischemia occurring in a series of 10 patients with malignancy after initiating treatment of deep venous thrombosis. Patients in this series also demonstrated a decline in platelet counts after stopping heparin, warfarin-associated supratherapeutic international normalized ratios (INRs), and evidence of persistent thrombin generation despite anticoagulation.

Topics: Anticoagulants; Female; Gangrene; Humans; Ischemia; Leg; Male; Neoplasms; Venous Thrombosis; Warfarin

Topics: Aged, 80 and over; Anticoagulants; Antiphospholipid Syndrome; Extremities; Female; Gangrene; Humans; Thrombosis; Warfarin

A 35-year-old man developed priapism with the use of low-molecular-weight heparin and warfarin following repair of left brachial artery sustained after gunshot injury. Priapism progressed to penile gangrene despite decompression and distal shunt procedure leading to total penectomy and perineal urethrostomy. We describe the mechanism of anticoagulant (heparin and warfarin)-induced penile gangrene and the possible methods to avert such a devastating complication.

Topics: Adult; Anticoagulants; Brachial Artery; Dalteparin; Drug Therapy, Combination; Gangrene; Hemopneumothorax; Humans; International Normalized Ratio; Male; Penis; Perineum; Postoperative Care; Postoperative Complications; Priapism; Saphenous Vein; Thrombosis; Ultrasonography, Doppler, Color; Urethra; Warfarin; Wounds, Gunshot

This unfortunate patient case highlights the problems with "overdiagnosis" of HIT. Despite "positive" tests for HIT antibodies, the low pretest probability for HIT and the known propensity of patients with APS to yield false-positive HIT antibody results suggests that the patient did not have a true diagnosis of HIT. Moreover, the early administration of warfarin and the choice of argatroban for parenteral anticoagulation when monitoring was hindered by a prolonged baseline aPTT likely play a key factor in the progression of UE DVT to VLG. Ironically, the problems of anticoagulant monitoring posed by the prolonged baseline aPTT likely contributed to the subsequent overanticoagulation and fatal pulmonary hemorrhage. With benefit of hindsight, avoiding the temptation to test for HIT in a low pretest probability situation, and treatment with either heparin using anti-factor Xa monitoring or with non-aPTT-monitored therapy such as LMWH or fondaparinux would likely have resulted in a more favorable clinical course.

Topics: Anticoagulants; Antiphospholipid Syndrome; Arginine; Diagnostic Errors; Drug Monitoring; Fatal Outcome; Female; Gangrene; Hemorrhage; Humans; Lung Diseases; Middle Aged; Pipecolic Acids; Sulfonamides; Thrombocytopenia; Upper Extremity; Vascular Diseases; Warfarin

Topics: Anticoagulants; Blood Coagulation Disorders; Endocarditis; Gangrene; Humans; Male; Middle Aged; Neoplasms; Palliative Care; Risk Factors; Venous Thromboembolism; Warfarin

Topics: Aged, 80 and over; Anticoagulants; Cardiac Surgical Procedures; Coumarins; Extremities; Gangrene; Heparin; Humans; International Normalized Ratio; Male; Middle Aged; Necrosis; Thrombocytopenia; Vitamin K; Warfarin

Topics: Anticoagulants; Carcinoma, Signet Ring Cell; Female; Gangrene; Heparin, Low-Molecular-Weight; Humans; Lower Extremity; Lymphatic Metastasis; Middle Aged; Necrosis; Neoplasms, Unknown Primary; Purpura, Thrombotic Thrombocytopenic; Skin; Venous Thrombosis; Warfarin

Heparin-induced thrombocytopenia (HIT) is a common, often catastrophic, syndrome that produces the most hypercoagulable of states. Emerging therapeutic strategies use alternative anticoagulants; warfarin's place is being reexamined. Early in the course of warfarin therapy, there may be net procoagulant effects because of the inhibition of protein C. With HIT, it has been suggested that unopposed warfarin can precipitate venous limb gangrene. There are also reports of warfarin-induced skin necrosis. We seek to confirm and increase awareness of the risks of warfarin with HIT.. 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.. At warfarin initiation, 5 patients had recognized HIT and 1 had it recognized later. Complications emerged after 2 to 7 days, and consisted of warfarin-induced skin necrosis (n = 5) and venous limb gangrene (n = 2); 1 patient had both. This emerged with unopposed warfarin in 4 patients and as a direct thrombin inhibitor was being withdrawn in 2. All had supratherapeutic international normalized ratios. One patient required leg and breast amputations, and another one died.. Because of the early effects on protein C, warfarin can precipitate venous limb gangrene and/or skin necrosis in the extreme hypercoagulable milieu of HIT. With HIT, unopposed warfarin should be avoided and caution is needed during transition from a direct thrombin inhibitor. Warfarin should be initiated at modest doses in patients with HIT after platelet recovery. Implications extend to warfarin initiation with other thrombotic diatheses.

Topics: Adult; Aged; Anticoagulants; Drug Eruptions; Female; Gangrene; Heparin; Humans; Leg; Male; Middle Aged; Necrosis; Thrombocytopenia; Warfarin

A 53-year-old man with lung adenocarcinoma developed pulmonary embolism and bilateral popliteal venous thrombosis. Treated with intravenous unfractionated heparin and discharged home on warfarin, he returned a week later with extending thrombosis. Treatment with heparin followed by warfarin was reinitiated. Twenty-four hours following the re-administration of warfarin, the patient's INR increased to 14.5. The platelet count dropped by more than 50%, and he developed venous limb gangrene of the left leg and skin necrosis of the right leg. Heparin-induced thrombocytopenia was ruled out, and coagulation studies showed a severe depletion of protein C as well as increased thrombin generation. The patient was transfused with fresh frozen plasma, and vitamin K was given. Heparin was continued, and after 4 weeks, the patient improved markedly showing only minimal necrosis of the toes. Venous limb gangrene is a major complication associated with warfarin therapy. Its pathogenesis is explained by a transient hypercoagulable state produced by protein C depletion that leads to microvascular thrombi progressing to venous limb gangrene. The present case emphasizes the importance of careful anticoagulation with heparin followed by slow initiation of low-dose warfarin, in order to minimize thrombotic complications.

Topics: Adenocarcinoma; Anticoagulants; Fatal Outcome; Gangrene; Heparin; Humans; Male; Middle Aged; Popliteal Vein; Pulmonary Disease, Chronic Obstructive; Pulmonary Embolism; Thrombosis; Warfarin

We report two patients with deep-vein thrombosis complicating immune heparin-induced thrombocytopenia who developed venous limb gangrene during overlapping therapy with a direct thrombin inhibitor (lepirudin or argatroban) and warfarin. In both patients, therapy with the direct thrombin inhibitor was interrupted during persisting severe athrombocytopenia while warfarin administration continued. Both patients exhibited the typical feature of a supratherapeutic international normalized ratio (INRs, 5.9 and 7.3) that has been linked previously with warfarin-associated venous limb gangrene. These data suggest that warfarin anticoagulation be postponed in patients with acute heparin-induced thrombocytopenia until substantial recovery of the platelet count has occurred.

Topics: Aged; Aged, 80 and over; Amputation, Surgical; Anticoagulants; Arginine; Autoimmune Diseases; Catheterization, Central Venous; Contraindications; Drug Administration Schedule; Drug Therapy, Combination; Female; Gangrene; Heparin; Hirudin Therapy; Hirudins; Humans; International Normalized Ratio; Leg; Male; Middle Aged; Necrosis; Pipecolic Acids; Protein C Deficiency; Recombinant Proteins; Sulfonamides; Surgical Wound Infection; Thrombin; Thrombocytopenia; Thrombophlebitis; Warfarin

Vascular complications are frequent in long-term dialysis patients. The differential diagnosis is complex and includes immunological derangement (underlying disease, uremia), vasculopathic-atheroembolic diseases, calciphylaxis, infections, neoplasm, coagulation disorders, and adverse drug effects.. We report on a 50-year-old male patient with a long follow-up on renal replacement therapy (20 years), currently on daily hemodialysis. The patient's history of kidney transplantation was complicated by seven acute rejection episodes and by Kaposi sarcoma; comorbidity included HLA-B27 positive ankylosing spondylitis, diffuse vascular disease, recurrent atrial fibrillation, chronic hypotension, HCV positivity. Ten days after the start of warfarin for an atrial fibrillation episode, the patient developed digital necrotising ulcerations, rapidly evolving into partial symmetric digital gangrene at distal phalanxes. The timing and evolution of the lesions and the finding of protein S deficiency were the clues for diagnosing warfarin-induced skin necrosis (WISN); the drug was discontinued and therapy with low-molecular weight heparin, plasma and prostacyclin achieved slow resolution of lesions.. According to a combined MEDLINE and EMBASE search, this is the first report of WISN in a hemodialysis patient: underlining the clinical relevance of this uncommon problem, this case exemplifies the difficult differential diagnosis of acute vascular skin lesions in dialysis

Topics: Anticoagulants; Databases as Topic; Diagnosis, Differential; Dialysis; Fingers; Gangrene; HLA-B27 Antigen; Humans; Male; Middle Aged; Necrosis; Renal Replacement Therapy; Skin; Spondylitis, Ankylosing; Vascular Diseases; Warfarin

The cause of cancer-associated venous limb gangrene is unknown but could paradoxically be due to warfarin.. To determine the pathogenesis of venous gangrene in a patient with cancer.. Case report.. University hospital in Ontario, Canada.. 66-year-old woman with metastatic lung cancer and deep venous thrombosis.. Levels of vitamin K-dependent factors, additional coagulation factors, and thrombin-antithrombin complexes (marker of thrombin generation).. During warfarin use, venous limb gangrene developed when the international normalized ratio (INR) reached 6.0 (therapeutic range, 2.0 to 3.0); at this time, the level of protein C (a vitamin K-dependent natural anticoagulant) was severely reduced, but thrombin-antithrombin complexes remained markedly elevated. The supratherapeutic INR was explained by the greatly reduced levels of factor VII, which correlated closely with protein C levels; therefore, the high INR was a surrogate marker for severely reduced protein C activity.. Warfarin may contribute to the pathogenesis of cancer-associated venous limb gangrene by leading to severe depletion of protein C while at the same time failing to reduce thrombin generation.

Topics: Aged; Anticoagulants; Antigen-Antibody Complex; Blood Coagulation Disorders; Blood Coagulation Factors; Female; Gangrene; Humans; Lung Neoplasms; Protein C Deficiency; Thrombin; Thrombocytopenia; Venous Thrombosis; Warfarin

Topics: Aged; Anticoagulants; Antigen-Antibody Complex; Blood Coagulation Disorders; Blood Coagulation Factors; Female; Gangrene; Humans; Lung Neoplasms; Protein C Deficiency; Thrombin; Thrombocytopenia; Venous Thrombosis; Warfarin

Platelet-mediated arterial occlusion is a well-recognized cause of limb loss in patients with heparin-induced thrombocytopenia. However, the syndrome of distal ischemic necrosis complicating the deep venous thrombosis (venous limb gangrene) sometimes associated with heparin-induced thrombocytopenia has not been well characterized.. To study the pathogenesis of venous limb gangrene associated with heparin-induced thrombocytopenia.. Characterization (based on descriptive and case-control studies) of a novel syndrome of limb loss and hypothesis testing by analysis of plasma samples.. Five university-associated hospitals in one medical community.. Clinical and laboratory records of 158 patients with heparin-induced thrombocytopenia were reviewed to identify patients with venous limb gangrene (n = 8), limb arterial thrombosis (n = 10), and uncomplicated deep venous thrombosis (n = 58).. Clinical and laboratory factors associated with venous limb gangrene, including thrombin-antithrombin complexes and vitamin K-dependent procoagulant and anticoagulant factors.. Warfarin treatment was more frequently associated with venous limb gangrene than with limb arterial thrombosis (8 of 8 patients compared with 3 of 10 patients; P = 0.004). The anticoagulant effect of warfarin seemed greater in the 8 patients with venous limb gangrene than in the 58 patients who did not develop gangrene (median International normalized ratio, 5.8 compared with 3.1; P < 0.001). Compared with plasma from controls, plasma from patients with venous limb gangrene had a higher ratio of thrombin-antithrombin complex to protein C activity during warfarin treatment. No hereditable abnormalities of the protein C anticoagulant pathway were seen in any patient.. Warfarin treatment of deep venous thrombosis associated with heparin-induced thrombocytopenia is a possible cause of venous limb gangrene, perhaps because of acquired failure of the protein C anticoagulant pathway to regulate thrombin generation.

Topics: Adult; Anticoagulants; Case-Control Studies; Female; Gangrene; Heparin; Humans; Male; Middle Aged; Protein C; Thrombin; Thrombocytopenia; Thrombophlebitis; Warfarin

Topics: Anticoagulants; Gangrene; Heparin; Humans; Thrombocytopenia; Thrombophlebitis; Warfarin

Topics: Adult; Breast; Female; Gangrene; Humans; Warfarin

Topics: Diagnosis, Differential; Gangrene; Humans; Necrosis; Skin; Warfarin

Sodium warfarin is one of the most commonly used oral anticoagulants. It is not without complications. A case is presented of a 56-year-old woman on well-regulated sodium warfarin therapy who suffered unexplained necrosis and gangrene of the breast. She underwent total mastectomy for debridement because of the extensive nature of the infarction. Possible pathophysiological mechanisms for this process are discussed.

Topics: Breast; Female; Gangrene; Humans; Mastectomy; Middle Aged; Necrosis; Warfarin

Antithrombin III is a potent coagulant inhibitor in plasma. Congenital deficiency of antithrombin III may predispose to thrombotic events and may complicate surgical management. We describe a patient with congenital antithrombin III deficiency who developed superior mesenteric vein thrombosis after the cessation of warfarin therapy which resulted in venous gangrene of the small intestine. Initial treatment of this deficiency with fresh frozen plasma and subsequent long-term management with warfarin therapy has been effective in avoiding further thrombotic events.

Topics: Adult; Antithrombin III Deficiency; Blood Coagulation Disorders; Blood Transfusion; Child; Female; Gangrene; Humans; Intestine, Small; Male; Mesenteric Veins; Pedigree; Thrombosis; Warfarin

Skin and soft tissue necrosis is an uncommon but increasingly recognized complication of coumarin anticoagulant therapy. A patient is described with extensive involvement of all four extremities and the nose, requiring amputation of three extremities. The characteristic clinical features of the disorder are reviewed, with a discussion of the pathology, pathogenesis, and possible treatment modalities.

Topics: Aged; Connective Tissue; Extremities; Female; Gangrene; Humans; Necrosis; Nose; Skin; Warfarin

Topics: Endocarditis, Subacute Bacterial; Female; Gangrene; Humans; Male; Middle Aged; Prothrombin Time; Pulmonary Embolism; Skin Diseases; Warfarin

Topics: Adipose Tissue; Coumarins; Gangrene; Humans; Leg; Necrosis; Skin; Skin Diseases; Thrombophlebitis; Warfarin

Skin and soft tissue necrosis, in association with the coumarin derivatives, characteristically afflicts females between the third and tenth days of treatment. Anatomic regions abundant in subcutaneous fat are most commonly affected. Many of these patients have underlying serious medical problems. Three additional patients with tissue infarction complicating coumadin therapy are presented. Possible etiologic mechanisms are discussed, but the basic physiopathologic condition remains an enigma. Venous thrombosis can be a related clinical phenomenon. Treatment perspectives are outlined.

Topics: Adult; Coumarins; Female; Gangrene; Heparin; Humans; Infarction; Middle Aged; Necrosis; Pulmonary Embolism; Thrombophlebitis; Time Factors; Warfarin

Sodium warfarin was administered to a 59-year-old woman with congestive cardiac failure and deep vein thrombosis. After 3 days of therapy the nipple and areola of the left breast became inflamed; the entire breast then became necrotic. Gangrene spread and a simple mastectomy was performed. The patient died from pulmonary embolism 1 day after operation. Histologic examination of the breast revealed thrombi in some of the arteries and veins. The etiology of this condition is obscure, and there is no known way of preventing or effectively treating the condition. Simple mastectomy or more conservative local excision recommended.

Topics: Breast Diseases; Female; Gangrene; Humans; Middle Aged; Skin Diseases; Warfarin

Arterial emboli were extracted from 79 patients between 1955 and 1963 with polyethylene catheter suction systems and/or retrograde flushing and from 149 patients between 1963 and 1973 with Fogarty catheters. The Fogarty-era patients were older, had a greater incidence of ischemic heart disease, and presented with a greater degree of preoperative peripheral ischemia. The limb salvage rate of 87 percent after Fogarty catheter embolectomy was not statistically different from the salvage rate of 79 percent after suction catheter embolectomy, but the number of limbs with distal pulses postoperatively was significantly greater after Fogarty treatment, 64 vs. 42 percent. Delay in treatment and the presence of prior occlusive vascular disease adversely affected results in both eras. The in-hospital embolic recurrences occurred in 9 percent of the patients anticoagulated postoperatively and in 31 percent of those not anticoagulated. Heparin and warfarin were equally effective in preventing recurrences, but wound complications were seen in 33 percent of the heparinized patients, compared with 7 percent of those receiving warfarin and 4 percent of those not anticoagulated.

Topics: Aged; Aortic Diseases; Arm; Catheterization; Embolism; Femoral Artery; Follow-Up Studies; Gangrene; Heparin; Humans; Iliac Artery; Ischemia; Leg; Popliteal Artery; Postoperative Care; Recurrence; Warfarin

Topics: Anemia, Hemolytic; Breast Diseases; Disseminated Intravascular Coagulation; Female; Fibrin; Gangrene; Humans; Middle Aged; Necrosis; Thrombophlebitis; Warfarin

Although venous thrombosis (thrombophlebitis) is well known, there are uncommon manifestations which are seen infrequently, discussed rarely, and documented poorly. Experiences with 38 patients in seven categories are discussed in terms of our results and the pertinent reports of others. Pulmonary necrosis after embolic pulmonary infarction (six patients) may require tube thoracotomy and/or lung resection and contraindicate further heparin therapy. Iliac and/or femoral vein thrombosis occasionally fails to recanalize. Long-standing occlusion (18 patients) may be benefited by a cross-over saphenous vein graft. Left iliac venous occlusion secondary to pressure from the crossing right iliac artery (four patients) may indicate repair or bypass. Budd-Chiari syndrome (thrombosis of the hepatic venous outflow) was, in a single patient, carried past a critical period by a long Dacron tube shunt graft from the umbilical vein to the azygos vein. Subclavian and axillary venous thrombosis due to thoracic outlet pressure syndrome (three patients) often responds to heparin but may require thrombectomy; later resection of the first rib is indicated. Phlegmasia cerulea dolens (blue phlebitis) with tissue gangrene (three patients) requires immediate venous thrombectomy and subsequent heparinization. The occluded inferior vena cava (three patients) remains a challenging unsolved problem.

Topics: Adult; Aged; Arteries; Blood Pressure; Blood Vessel Prosthesis; Budd-Chiari Syndrome; Child; Female; Femoral Vein; Gangrene; Heparin; Humans; Iliac Vein; Male; Middle Aged; Necrosis; Pulmonary Embolism; Subclavian Vein; Thoracic Outlet Syndrome; Thrombophlebitis; Transplantation, Autologous; Veins; Vena Cava, Inferior; Warfarin

Topics: Aortic Valve Stenosis; Gangrene; Heart Valve Prosthesis; Humans; Male; Middle Aged; Skin Diseases; Warfarin

Topics: Aged; Anticoagulants; Arteriosclerosis; Arthritis; Breast Diseases; Female; Gangrene; Humans; Hypertension; Mastectomy; Middle Aged; Necrosis; Penicillins; Postoperative Complications; Thrombophlebitis; Warfarin

Topics: Aged; Breast Diseases; Female; Gangrene; Hemorrhage; Heparin; Humans; Middle Aged; Phenindione; Pulmonary Embolism; Thrombophlebitis; Warfarin

Topics: Acute Kidney Injury; Arteriosclerosis; Cholesterol; Embolism, Fat; Gangrene; Humans; Hypertension; Male; Middle Aged; Pancreatitis; Toes; Warfarin

Topics: Acenocoumarol; Anticoagulants; Coumarins; Dicumarol; Drug Therapy; Ecchymosis; Ethyl Biscoumacetate; Gangrene; Necrosis; Phenindione; Pulmonary Embolism; Purpura; Skin Diseases; Thrombophlebitis; Toxicology; Warfarin

Topics: Angina Pectoris; Anticoagulants; Carotid Artery Thrombosis; Diabetic Angiopathies; Fibrinolysis; Gangrene; Heart Failure; Humans; Myocardial Infarction; Raynaud Disease; Thromboangiitis Obliterans; Thromboembolism; Warfarin

Topics: Coumarins; Gangrene; Humans; Thrombophlebitis; Warfarin