Tidings from the Citadel: Warfarin in Dialysis

Warfarin Use and the Risk for Stroke and Bleeding in Patients With Atrial Fibrillation Undergoing Dialysis – Mitesh Shah et al. Circulation. 2014;129:1196-1203.

A retrospective cohort study

Population based cohort of patients > 65 years who were admitted in Canada – Quebec and Ontario with a primary or secondary diagnosis of atrial fibrillation. Used ICD-9/10 codes to determine diagnosis and complications such as bleeding and stroke complications. Drug prescriptions were identified by database in Canada where patients > 65 have prescription benefit. Warfarin use was identified by a filled prescription within 30-days of AF diagnosis

Patients
626 dialysis patients and 204,210 nondialysis patients. Did not separate by stages of CKD, but rather HD or non-HD. Dialysis patients were younger, male, CHF, HTN, DM, CAD, and bleeding history.

Dialysis vs Non-Dialysis: CHADS2 >/= 2: 72% versus 55% (indication for anti-coagulation); HAS-BLED >/=3: 85% versus 25%. Similar rates of warfarin prescription (46% vs 51%)

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Stroke
In non-dialysis patients, warfarin users had a lower incidence of stroke (2.19 vs 2.51/100 person-years)

In dialysis patients, stroke incidence was similar for warfarin and non-warfarin users: 3.37 versus 2.91/100 person-years.

After adjusting for confounders – warfarin use had a HR of 1.14 in diaylsis patients. While in non-dialysis patients had a HR 0.87 with warfarin use.

Bleeding
After adjusting for confounders, warfarin use, was associated with a 44% higher risk for bleeding event in dialysis patients and 19% higher risk in nondialysis patients.

 

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Flea Bytes: Calf DVTs

Randomized double blind placebo-control trial that faced slow recruitment thus faces the problem of being underpowered to detect a difference.

Outpatients without cancer or prior VTE with symptomatic calf DVT. Assigned 1:1 to receive nadroparin or placebo daily for 6 weeks. All were given compression stockings and followed for 90 days.

Primary outcome was extension to proximal vein, contralateral proximal DVT, or systemic embolism by day 42.

Safety outcome – non-major bleeding by day 42.
122 patients in nadroparin and 130 placebo.

Primary outcome 3% in the nadroparin and 5% in placebo. 5 patients had bleeding in nadroparin arm with 1 major bleeding event.

Need more information before change in practice.

Anticoagulant therapy for symptomatic calf deep vein thrombosis (CACTUS): a randomised, double-blind, placebo-controlled trial – M Righini et al; Lancet Haematology, The, 2016-12-01, Volume 3, Issue 12, Pages e556-e562.

Flea Bytes: Paracentesis and Bleeding Risk

AASLD Practice Guidelines:

Bleeding from paracentesis is relatively uncommon. The routine use of FFP or platelet transfusion is not recommended before paracentesis. You should avoid any engorged veins as most bleeding occurs from the venous circulation.

It may be reasonable to correct patients who have bled before with paracentesis, have hyperfibrinolysis (as they wouldn’t be able to clot effectively due to factor depletion), patients with evidence of overt bleeding from mucosa (epistaxis, vaginal bleeding, etc), or have history of bleeding at puncture sites (like IVs or blood draws).

Reference:

“Management of adult patients with ascites due to cirrhosis: an update.” Runyon BA. Hepatology. 2009;49(6):2087 

Flea Bytes: Differentiating Synthetic Dysfunction from DIC in Liver Disease

You can check factor VIII levels because they tend to be normal to increased in liver disease as it is not produced by the liver, but rather endothelial cells. In DIC all of the factors are consumed, so factor VIII levels will be low.

The other test that maybe helpful is checking a d-dimer. The d-dimer tends to be significantly increased in DIC due to profound fibrinolysis. However, d-dimer levels may also be elevated in liver disease, but usually only mildly elevated.

Flea Bytes: Apixaban in Severe Renal Failure

In 2014, the FDA approved the label change for apixaban to include dosing recommendations for patients with severe renal failure or on hemodialysis. Previously the labeling stated that there was no data to inform the use of apixaban in patients with creatinine clearance < 15 or on dialysis. The data with which this change was made was sparse.

We know that 27% of the drug is eliminated unchanged by the kidneys.

There was a small single dose pharmacokinetic study of 8 patients on dialysis. Dialysis removed 14% of the drug. This study found a drug exposure area under the curve increase of 36%. Importantly, there was no data collected to inform the clinician the effects of repeated doses of the drugs and the possibility of drug accumulation.

I would not recommend apixaban as a first line anticoagulant in ESRD, but in cases where options are limited and risks and benefits are discussed with the patient – it may be reasonable to use based on the above information.