Limb gangrene in cancer patients receiving warfarin

November 10, 2015

Venous limb gangrene can occur in cancer patients, but the clinical picture and pathogenesis aren’t clear.

Anna GarrettVenous limb gangrene (VLG) can occur in cancer patients, but the clinical picture and pathogenesis aren’t clear. A recent clinical report identified 10 patients with metastatic cancer (seven pathologically proven) who developed severe venous limb ischemia after beginning treatment for deep-vein thrombosis (DVT). Cancer was not known or suspected in eight of the patients at presentation.

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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 heparin cessation.

Despite supratherapeutic INRs, patient plasma samples contained markedly elevated thrombin-antithrombin (TAT) complex levels (indicating uncontrolled thrombin generation) and protein C depletion. This profile is similar to what is seen in patients with warfarin-associated VLG complicating heparin-induced thrombocytopenia.

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Analyses of vitamin K-dependent factors in six of the 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 protein C.

The authors concluded 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. 

Source: Warkentin TE, Cook RJ, Sarode R et al. Warfarin-induced venous limb ischemia/gangrene complicating cancer: A novel and clinically distinct syndrome. Blood. 2015; 126:486–493.

Lower SBP reduces AF risk in hypertensive patients

The incidence of atrial fibrillation (AF) is higher among patients with hypertension. In a substudy of the LIFE trial, researchers evaluated whether achievement of lower systolic blood pressure (SBP) during treatment of hypertension would be associated with a decreased risk for new-onset AF.

The trial included 8,831 hypertensive participants who had electrocardiographic (ECG) evidence of left ventricular hypertrophy and no history of AF. During follow-up (mean, 4.6 years), 701 patients experienced new-onset AF (7.9%). These patients were older than non-AF patients; more likely to be male and nonblack, and to have histories of ischemic heart disease, myocardial infarction, stroke, and heart failure. They were also more likely to have lower total cholesterol levels and greater albuminuria; and less likely to have been randomized to losartan in the original LIFE trial.

Patients with lower blood pressure (<130 mm Hg) were 40% less likely to develop AF than patients classified with less-adequate (≥142 mmHg) control and 24% less likely to develop AF than the cohort classified with “typical” (131-141 mm Hg) control. In multivariate analyses that adjusted for treatment randomization and cardiovascular factors, both lower and typical SBP values were associated with statistically significant lower risk for new-onset AF.

Source: Okin PM, Hille DA, Larstorp AC, et al. Effect of lower on-treatment systolic blood pressure on the risk of atrial fibrillation in hypertensive patients. Hypertension. 201;66:368–373.



USPSTF updates aspirin recommendations for CVD and colorectal cancer prevention

In a draft statement, the U.S. Preventive Services Task Force (USPSTF) is recommending low-dose aspirin to prevent both cardiovascular disease and colorectal cancer in adults ages 50 to 59 years who have a 10-year CVD risk of 10% or greater (Grade B).

Patients ages 60 to 69 should talk to their clinicians about whether the benefits of daily aspirin outweigh the risks (grade C). Patients using aspirin as a preventive must have a life expectancy of at least 10 years and be willing to take it daily for that length of time.

The USPSTF notes that patients at increased risk of bleeding shouldn't use daily aspirin. The task force says there is insufficient evidence to make a similar recommendation for adults younger than 50 years or older than 70 years (both grade I statements). The task force previously published separate recommendations on aspirin use for preventing CVD (2009) and colorectal cancer (2007).

This is the first time that a major medical organization in the United States has recommended aspirin for the primary prevention of colorectal cancer in average-risk adults. The American Cancer Society recommends against the use of aspirin as a prevention strategy for colorectal cancer.

Source: U.S. Preventive Services Task Force. Accessed September 20, 2015.