Normal Limits

"Chance is the very guide of life"

"In practical medicine the facts are far too few for them to enter into the calculus of probabilities... in applied medicine we are always concerned with the individual" -- S. D. Poisson

November 02, 2005

Medscape News - Presence of Heparin Antibodies Predicts Morbidity After Cardiac Surgery (Kress et al 2005)

Dr. David Kress, a thoracic surgeon at Aurora St. Luke's Medical Center in Milwaukee, Wisconsin, reported at the American College of Chest Physicians annual meeting:
Testing positive for heparin/platelet factor 4 (HPF 4) [antibody] is an independent predictor of complications associated with cardiac surgery, with or without heparin-induced thrombocytopenia (HIT), according to a retrospective study presented here at a late-breaking session during CHEST 2005, the annual meeting of the American College of Chest Physicians.

This was a retrospective study of 1114 patients at Aurora St. Luke's who underwent cardiopulmonary bypass.
[The 60 patients (5.4%) who tested positive] had an elevated incidence of acute limb ischemia (5.0% vs 0.9%; P = .03) and a higher incidence of renal dialysis (11.7% vs 4.3%; P = .02), gastrointestinal complications (15.0% vs 5.7%; P = .01), and prolonged ventilation exceeding 96 hours (21.7% vs 8.8%; P = .01).

Some of the weaknesses of this study is of course the retrospective design. The presence of HPF4 antibody may be associated with higher risk simply because it is a marker for higher co-morbidity.

Previously HPF4 antibody is associated with the development of HIT Type 2. Typically these cases arise 5 to 10 days after initiation of heparin anti-coagulation, and come to attention by the dramatic 30% to 50% drop of platelet levels. The disturbance of the intricate balance in the coagulation system can be lead to the formation of lethal arterial or venous clots.

There are isolated reported cases of HIT associated with mere IV heparin flushes (Heparin-induced thrombocytopenia (HIT) due to heparin flushes: a report of three cases by Kadidal et al in Journal of Internal Medicine, 2001.)

Currently, HIT is a "clinicopathological" diagnosis. That is, it is made "most confidently" when the patients exhibit an otherwise unexplained episode of thrombocytopenia and has serum HPF4 antibodies. Dr. Theodore Warkentin has a detailed article on the diagnosis of HIT. It also provides a nomogram for diagnosis appropriate for post-cardiac surgery patients only.

While the treatment of HIT in immediate discontinuation of heparin and replacement with substitutes such as Lepirudin, Argatroban, and Danaparoid. However, as noted in the Medscape article, there is not sufficient data on the use of these alternatives in cardiopulmonary bypass.

This report is remarkable in suggesting an adverse effect of HPF4 antibody in the absence of the salient signs of HIT. A search through PubMed revealed that a case-control study of patients in a Pediatric ICU also showed an analgous finding. Specifically, it found an association between having anti-HPF4 antibody levels and developing thrombosis, in the absence of thrombocytopenia. (no time to read original article, sorry)

By let me re-iterate: Some of the weaknesses of [the Kress et al study] is of course the retrospective design. The presence of HPF4 antibody may be associated with higher risk simply because it is a marker for higher co-morbidity. I'm looking forward to reading the article when it gets published to see how this is accounted for.

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