Prophylactic Anticoagulation Can Cause More Morbity And Mortality Than It Prevents

The recent exchange in the “Letters to the Editor” between Dr. Sarmiento(1) and Drs. Westrich and Sculco(2) regarding prophylaxis against thromboembolic disease raises the question, in my mind at least, whether prophylaxis with anticoagulants kills more patients than it saves.

Two personal experiences with patients who died as consequence of anticoagulation has caused me to raise this question. The more recent patient was a 69-year-old man with cirrhosis of the liver who sustained a hip fracture, underwent prosthetic replacement, was treated with prophylactic low molecular weight heparin and died of a massive GI bleed 3 days later. I asked the medical consultant who had ordered the prophylaxis regimen why he anticoagulated a patient with cirrhosis and potential bleeding tendencies His answer was that physicians are sued if one of their patients expires from thromboembolism but are not considered liable if the cause of death is a GI bleed. Unfortunately, this rather cynical approach is justified because of one "local expert" in Florida is convinced that any patient who dies of thromboembolism is the responsibility of the treating physician and is willing to so testify.

The second case was a physician and personal friend who died from subarachnoid hemmorage while on anticoagulants. Of course, no medical liability was ever considered.

As Sarmiento commented, the practice of prophylactically anticoagulating our orthopaedic patients is accompanied by a relatively high prevalence of complications. These complications seem to be more evident in the non-orthopaedic literature than in company sponsored studies generally published in the orthopaedic literature. For example, a study on “Incidence of Adverse Drug Reactions in Hospitalized Patients” estimated that fatal drug reactions occurred in 93,000 patients per year making ADR’s somewhere between the fourth and seventh leading cause of death in the United States.3 These authors point out that many of the drugs being used for patients, such as anticoagulants, carry an unavoidable high toxicity. Other authors(4), (5) studying major bleeding after treatment for deep venous thrombosis report 4% of patients are readmitted within 90 days. This contrasts with studies in the orthopaedic literature which generally report a very low (0.9%) rate of “major” bleeding complications within 3 months after total hip replacement.6

Another risk of prophylactic anticoagulation not evident from the orthopaedic literature is the relatively common complication of heparin induced thrombocytopenia occurring in 1-3% of patients treated with heparin.(7) This antibody mediated drug reaction is paradoxically often associated with an increased thrombosis and is most commonly seen in patients who have received heparin within the previous 100 days. This may well explain some of the problems of thromboembolism occurring despite apparently well maintained anticoagulation and perhaps some of the thromboemboli occurring after anticoagulation is halted.

These fairly common difficulties with anticoagulation are really never discussed in most of the large scale clinical orthopaedic studies of prophylaxis, which by necessity are supported by the manufacturers of the anticoagulants. In addition, there never seems to be any mention of death, either directly or indirectly from bleeding as a result of the anticoagulation. This is, in spite of the fact, that bleeding does cause fatal complications from GI bleeding or cerebral hemorrhage as in my two patients or indirectly causes significant morbity due to infected joints secondary to hematoma formation.(7, 8,9,10)

The basic principle of doing no harm or doing the least harm possible applies to this issue. Sarmiento’s letter points out that rapid mobilization of patients to avoid prolonged sitting either in a chair or in bed,and emphasizing active exercises of thigh and leg muscles is indeed a valid prophylaxis method. In this litigious age the claim of experts that any patient suffering from thromboembolism is not receiving the standard of care is true hubris. The question, “what is the standard of care?” must be measured by both the risks and the benefits of prophylaxis and recognition that anticoagulation carries an unavoidable morbity and mortality for many patients.

References:

1. Sarmiento A: Letter to the Editor. Prophylaxis against venous thromboembolic disease: Costs and controversy. JBJS 84A:2305-2307, 2002 2. Westrich G, Sculco T: Reply, Letter to the Editor. JBJS 84A:2305-2307, 2002 3. Lazarou J, Pomeranz B, Corey P: Incidence of adverse drug reactions in hospitalized patients. JAMA 279:1200-1205, 1996 4. Bates S, Ginsberg J: Bleeding after initiation of anticoagulant therapy for deep vein thrombosis. Am J Med 107(5):414-424, 1999 5. White R, Beyth R, et al: Major bleeding after hospitalization for deep -venous thrombosis. Am J Med 107(5):517-8, 1999 6. Colwell Jr CW, Collis DK, et al: Comparison of enoxaparin and warfarin for the prevention of venous thromboembolic disease after total hip arthroplasty. Evaluation during hospitalization and three months after discharge. JBJS 82(9):1362-3, 2000 7. Warkentin TE, Kelton JG: Temporal aspects of heparin-induced thrombocytopenia. New Engl J Med 344(17):1286-1292, 2001 8. Berwaerts J, Robb O, et al: Course, management and outcome of oral- anticoagulant-related intracranial hemorrhages. Scottish Med J 45(4):105- 9, Aug 2000 9. Zielinski C: Letter to the Editor. Hematoma as a complication of enoxaparin use. JBJS 82A:1362-1363, 2000 10. Colwell C, Collis D, et al: Reply, Letter to the Editor. JBJS 82A:1363, 2000