Eying the Event Horizon

World War II fighter pilot aces were not only damn good shots but they also had what is called situational awareness. They could concentrate on the enemy aircraft in their sites in front of them but also have a sixth sense about what was going on around them and if there was an enemy looking to get behind them. They had to watch their 6 along with everything else. When clinicians care for sick patients it is also important for them to have situational awareness. I will again mention the pulmonary embolism issue which is a blood clot in the lungs.

If a health care provider seeing a patient feels strongly that the patient may have a pulmonary embolism, they may want to start treatment immediately. The earlier the treatment is started for this potentially life threatening disorder the better. However, sometimes patients may be too sick to be transported safely and undergo the definitive test for this called a spiral CT scan. If their kidneys are not working up to par, a common finding in critically ill patients, this also is a reason to not be able to get this test. Starting treatment makes sense there if is a high index of suspicion and when a definitive diagnosis cannot obtained in a timely manner. The test can be done at a later time when it is safer.

The first option in treating a pulmonary embolus is usually thinning the blood (anticoagulation) with one of many available drugs. Coumadin is one such commonly known drug that thins the blood but it is not used first because it may take days to get the necessary effect and there are risks that it may worsen the potential for further clot formation when it is the only drug started.  Another well-known drug is heparin. This is given by intravenous infusion and historically this has the drug that has been used when needing to start treatment for clotting disorders that includes pulmonary embolism.

There are several newer agents that in some cases have been shown to be better than that old standby, heparin. These new agents include enoxaparin (Lovenox), daltaparin (Fragmin), and fondaparinux (Arixtra). There are several advantages to these agents. Heparin is usually given by continuous intravenous infusion (IV drip) and has to be adjusted to target a narrow range of blood thinning. These new agents are given by one shot at a time injection, not by continuous infusion, and do not requiring regular monitoring of how thin the blood is as with heparin. Typically with heparin, there is a large (loading) dose given followed by the infusion. There are no loading doses with these newer agents and they are given by scheduled injection ranging from every twelve to twenty four hours. So, one dose given, no continuous infusions, no frequent blood draws to monitor how thin the blood is, and no adjustments to dosing once the drug is started. This all sounds great except there is a big problem with these newer agents.

There is that famous phrase by Donald Rumsfeld, the Secretary of Defense under George W. Bush, about known knowns, known unknowns and unknown unknowns in describing the Iraq War. This all applies to medicine and to especially sick patients. The situational awareness comes in when stepping back and going down the path of starting anticoagulation (a blood thinner) in a sick patient. The known knowns are the known history of the patient. The big risk of all these agents is bleeding and if there is something in the history that places the patient at high risk for bleeding then starting blood thinners may not be such a good idea. This all needs to be thought through before starting one these drugs. And yes there are alternatives to blood thinners in such patients. The known unknowns are those patients that may have a bleeding risk but it may be worth it to start anticoagulation anyway-balancing risk and benefit. The last are the unknown unknowns and in the spirit of really sick patients harboring all kinds of potential problems, even when there is no history of potentials for bleeding, there still may be bleeding when one of these agents are started.

The other unknown unknown is that it is difficult to predict which sick patient may get sicker.  A patient may be admitted to a hospital in stable condition and become unstable and critically ill. When one reads or hears of such patients in the media, the term commonly used is, ‘critical’. Stabilizing these unstable patients in the ICU sometimes requires performing invasive procedures which carry risks of, you guessed it, bleeding. If a patient has a dangerously low blood pressure, they may require placement of a special catheter called a central line. These lines are best placed in a large vein typically either in the neck (internal jugular vein) or in the chest (subclavian vein). These catheters permit measurement of pressure and oxygen inside the veins in the chest that can aid in helping to stabilize the patient. They can also permit intravenous infusions of drugs to treat low blood pressure and which can only be given safely through these large central veins. A patient with a suspected central nervous system infection may need a spinal tap. A risk of these invasive procedures is bleeding and anticoagulation substantially increases this risk. In most instances, anticoagulation would preclude doing invasive procedures.

The situational awareness comes in with bearing all of this in mind when deciding whether to anticoagulate a patient and which agent to use. If a clinician is worried about bleeding but thinks it is reasonable to treat (the known unknown) then this may be okay. They would bite the bullet so to speak and not only watch very closely for bleeding but also have a plan if this complication arises. Again, this requires thinking ahead and anticipating likely problems. If a patient is critically ill or it is thought they may become so, than this also needs to be born in mind in deciding anticoagulation and what agent to use in terms of prior planning to cover for this. Then there are the unknown, unknowns which a provider will know nothing about other than again forcing the issue to plan too for this contingency.

All of these new blood thinning agents are essentially irreversible; there is no way to reverse their blood thinning properties short of letting the drug wear off (enoxaprin is partially but mostly not reversible). Remember these are given at twelve to twenty four hour intervals and it is at least these time intervals that must lapse before their effects are gone. Bleeding with one of these drugs on board can be a disaster. These agents also significantly increase the risk of bleeding with invasive procedures which otherwise could be life-saving. However, there is a solution to this quandary.

Heparin, that old standby, marred with the inconvenience of continuous intravenous infusion, frequent blood draws and dose re-adjustments of the infusion rates is by far a safer agent in instances where there is risk of bleeding. It can be shut off with its effect dissipating in four to six hours but more importantly, it has an antidote, called protamine that can reverse its effect in a matter of minutes.

If an otherwise healthy patient has a blood clot or pulmonary embolism, then these newer agents certainly have a role in the initial treatment of blood clots. Again, such a patient will likely have a very low risk of bleeding with the clinician not anticipating a need for invasive procedures over the short time it takes to initiate treatment. Unfortunately, blood clot disorders tend to occur in more complicated and sicker patients. Having crashing patients admitted or transferred to the ICU with one of these irreversible agents on board really complicates providing life-saving treatment. Ironically, sometimes with starting one of these agents empirically as described above because the patient is strongly suspected of having a blood clot, the patient ends up not having one but still is critically ill. If a clinician suspects a clot and wants to start treatment but there is a possibility for bleeding or if the patient is sick or has the possibility for getting really sick, then heparin is probably the safer choice.



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