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Blood clot formation is a complex process involving first the accumulation of cells in the blood called platelets to form a plug and then a number of proteins/enzymes also called clotting factors that act upon one another in a specific sequence one after the other like dominoes dropping called a cascade to form a mesh that reinforces the platelet plug. The end result of which we see and call a clot. The platelets are the white circles in the video below. The cascade allows immense production of clot in a shorter period of time from a small amount of initiating stimulus so it has been programmed into our systems through evolution i.e.the organism that can stop bleeding the quickest after injury has the best chance of surviving. Along the way there are built in inhibitory enzymes at different parts of the cascade so that the cascade does not get out of control and turn your bloodstream into a solid clot.
Normally this clot formation process helps healing after cosmetic surgery and works in the background unnoticed for the benefit of patient and surgeon. It becomes a problem when the blood can form clots too easily or will not form clots or the clots form but are destroyed too quickly by the body. All of these situations can be dangerous for any type of surgery. These conditions can occur because of something the patient was born with, a disease the patient developed, a side effect of certain medications or a vitamin K deficiency. If it is medication induced the patient just stops or substitutes the medication sometime before surgery. In urgent or emergent cases another medication can be given to reverse the action of the first such as vitamin K for coumadin and protamine for helparin. Most of the blood clotting factors are manufactured in the liver so liver disease can result in the loss of this manufacturing ability resulting in a bleeding disorder.
Hemophilia is a classic case of an inability to form clots. It is caused by a deficiency or absence of some of the factors required for the clotting cascade to proceed and is something one is born with. They form the initial platelet plug but then cannot reinforce it. The defective gene is on the X chromosome so XX females tend to be carriers with only one affected X chromosome and their XY male sons can actually have the disease. In these cases the patient only needs to be injected with the missing clotting factors after which they can proceed with cosmetic surgery like any other patient. The injection is given 2 hours before surgery to raise the level of factor to 80% or more of normal and then maintained by additional injections for 10 to 14 days after surgery.
There is another form of hemophilia called Von Willebrand's Disease which involves defects on chromosomes other than the sex chromosomes X and Y. The bleeding tendencies are usually less in these cases than regular hemophilia but the severity of the bleeding disorder is highly variable. These patients have difficulty forming the initial platelet plug. The treatment of choice for mild von Willebrand disease is Stimate® or desmopressin acetate (DDAVP), a nasal spray that stimulates the body to increase factor VIII and von Willebrand levels. It is given to patients to increase the amount of the von Willebrand factor long enough for surgery or dental procedures to be performed. DDAVP is a synthetic product that carries no risk of infectious disease because it is not isolated from the blood of other individuals.
For excessive bleeding in Von Willebrand's Disease, infusions of a factor VIII concentrate rich in von Willebrand factor, such as Humate-P®, Alphanate®, Wilate® or Koate DVI®, may be required. Humate-P, manufactured by CSL-Behring, Alphanate, manufactured by Grifols and Wilate, manufactured by Octapharma are the only FDA-approved Factor VIII concentrate for use in von Willebrand Disease. The level should be raised to 80% or more of normal and maintained at that level for 10 to 14 days after surgery
Aspirin and many of the drugs used for pain can aggravate bleeding because they interfere with platelet function. People who have von Willebrand disease can take tylenol for pain relief because it does not inhibit platelet function. They should avoid any aspirin containing medications.
At the bottom of the cascade prothrombin is converted into thrombin which in turn converts fibrinogen to fibrin. Fibrin is the white hair like strands visible in the video above that form a mesh around the platelet plug so the clot does not come apart. The visible clot that we see with the naked eye consists of multiple fibrin molecules stuck together with cells called platelets that group together to form a plug at the site of injury.
Tranexamic acid, a synthetic derivative of the amino acid lysine, inhibits the activation of plasminogen to plasmin (visible in the bottom right corner of the cascade diagram above) and therefore prevents the destruction/degradation of fibrin. It is used in surgery that is associated with lots of bleeding (heart surgery, orthopedic surgery, craniofacial surgery, dental procedures in individuals taking blood thinners) to decrease the amount of blood loss by as much as 50% thereby decreasing the need for blood transfusions. It is also helpful for hemophiliacs who are actively bleeding and women with excessive menstrual bleeding. It is available in pill, injectable and mouth wash forms. The mouth wash form is effective for dental procedures performed on hemophiliacs as well as patients taking blood thinners.
Antithrombin III is a protein in the blood that binds to thrombin or other protein/enzymes at the bottom of the cascade to put the brakes on, stop or slow the clotting cascade. Patients who have antithrombin III deficiency are prone to making too much clot. They form clots in the deep veins of the legs and large veins in the abdomen. This can be precipitated by surgery, trauma, pregnancy, oral contraceptive use, or infection. These patients are given a medication called heparin to increase the activity of whatever amount of antithrombin III is present. Since the 1980s a purified (low molecular weight) heparin has been available that is easier to take and does not have to monitored as closely for overdose. This form can be taken at home instead of being restricted to in hospital use. They can also be given Antithombrin III concentrate to bring the blood levels to normal or close to normal.
Protein C and S inhibit the pathways involved in clot formation specifically at Factor VIII and Factor V. Individuals with genetic deficiencies of these proteins are also more prone to making clot than normal (6 times more so than individuals with normal protein S levels) especially in the veins. Protein S deficiency can be hereditary or due to vitamin K deficiency, sex hormone therapy, liver disease or chronic infections. Inherited Protein S deficiency occurs in 1 in 500 people in the US. Those who also are inactive, have a previous history of blood clots, smoke, are obese or are taking birth control pills are at a very high risk for forming blood clots. Protein S deficient patients therefore need to exercise regularly, stop or never start smoking, control their weight and stay away from birth control pills.
The primary goal in protein S deficient patients is to prevent the first big clot. Once that forms future ones are much more likely to form. Surgery can damage blood vessels stimulating the clotting cascade which in these cases can over react to the surgical stimulus. If the over reaction is severe enough it can be life threatening.
These patients need prophylactic anticoagulation with heparin before, during and after surgery with a hematologist directly involved in their care. In contrast to protein C and antithrombin, there is no purified form of protein S available for clinical use. Therefore surgery in these cases must be done in a hospital in case fresh frozen plasma (FFP) is required in the event that the clotting cascade starts to over react. That is the only way to replenish the Protein S stores. Surgery in an office operating room is not safe for these patients.
Aspirin changes the platelet surface so the platelets cannot stick together to form the initial platelet plug. If a blood vessel is then cut it will continue to leak blood for a prolonged period of time. This is why even removing a skin surface mole can be a problem in patients taking aspirin. Cutting into the skin and performing surgery on deeper structures in patients taking aspirin can be very dangerous. Even liposuction, which involves skin incisions only followed by introduction of a blunt metal tube to remove the fat should not be performed on patients who have recently taken aspirin. It takes 7 to 10 days for your body to make new platelets to replace those that have been altered by aspirin. It is you crucial that you stop any aspirin intake a week or more before any surgery. Even one aspirin in that time frame can cause a problem. The only other way to reverse the effect of aspirin is to transfuse platelets (a blood transfusion). With aspirin use the platelet count will be normal but they do not function properly. The only way to pick this up is by the patient telling the surgeon they took aspirin and by a test called a bleeding time. All the other usual blood tests will be normal.
Bleeding problems can also arise if the number of platelets is too high or too low. This situation can be caused by cancer, infection, chemotherapy, radiation, poisons, medications, nutritional deficiencies... Low platelet counts can be divided into those due to decreased production of platelets and those due to increased destruction of platelets. The normal platelet count is 150,000 to 400,000/mm3. Surgical bleeding becomes a problem with platelet counts less than 50,000/mm3. Spontaneously bleeding occurs at platelet counts less than 10,000/mm3. There are also conditions where the platelet count is very high (above 1,000,000/mm3) that are associated with abnormal bleeding during surgery. In such cases the platelet count has to be lowered before undergoing surgery. The life span of a normal platelet is 10 days. A transfused platelet has a life span of only 4 or 5 days. The treatment for abnormal platelet counts will depend on the cause of the problem.
As I mentioned in a previous blog vitamin E and multiple herbal medications prevent blood from clotting normally and can be very dangerous when combined with surgery.
One of my patients had a history of blood clots in the deep veins of his legs. This is particularly dangerous because the large clots can travel up to the heart and then onto the lungs. With the aid of his internist he received low molecular weight heparin around the time of his abdominoplasty and sailed through surgery without complications.
Another patient had a stent placed in a neck artery feeding directly into the brain. She was taking blood thinners to prevent clotting within the stent. Again with the aid of her medical doctors we stopped the blood thinners a week before surgery and started low molecular weight heparin. I removed a skin tumor from her scalp and she went back on the blood thinners a day after surgery.
I reviewed a case where a hemophiliac underwent facelift surgery. That patient was transferred directly from the surgeon's office operating room to a hospital operating room where blood components had to be transfused emergently until the bleeding stopped. After a couple of days in the intensive care unit that patient was sent home.
The bottom line is if there is an intrinsic problem with the ability to form clots cosmetic surgery that could result in significant bleeding should be done in a hospital with a hematologist familiar with the patient readily available. That way should the need arise for transfusing blood components or specialty care they are readily available. Safety during surgery should take precedence over cost of surgery.
Addendum November 18, 2012:
As mentioned above on the other side of the coin are patients who too readily form blood clots and do so while on the operating table under general anesthesia. If these clots form in the large veins of the lower abdomen, pelvic area or legs they can travel up to the lungs and because of their size kill the patient when they reach the lungs or heart. For decades the only solution to this problem was surgically placing a filter in the largest vein prior to its reaching the heart because the anticoagulation used to treat this precluded any surgery. That changed about 20 years ago with the introduction of an injectable low molecular weight heparin which dissolved older clots but did not prevent new clots from forming at the site of surgery.
The factor Xa oral anticoagulant Rivaroxaban was FDA-approved to reduce the risk for of clot formation in the large veins of the lower abdomen, pelvic area or legs and the migration of these clots into the lungs (DVT and PE) after knee or hip replacement surgery in July 2011. In November 2011 it was approved to reduce the risk for stroke in people with the heart condition nonvalvular atrial fibrillation. On November 2, 2012 its approval was expanded to include treatment of deep vein thrombosis (DVT) or pulmonary embolism (PE) and to reduce the risk for recurrences after initial treatment that is to say it can now be used for treatment as well as prevention. This is the first oral anti-clotting drug approved to treat and reduce the recurrence of blood clots since the approval of warfarin (coumadin) nearly 60 years ago. Now my abdominoplasty patient and skin tumor patient can take a pill before surgery instead of skin injections to prepare them for surgery.
Aaron Stone MD - Plastic Surgeon Los Angeles
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