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Anticoagulation in microsurgery

Success in microsurgery requires intact circulation via microvascular blood vessel anastomoses. Although the clotting mechanism prevents injured tissues from bleeding, it can be disruptive to a microvascular repair - inhibiting blood flow and promoting flap failure. 

Many factors are involved in the development of clots and include:

  • Vessel injury from trauma, hematoma and external pressure on vessels
  • Tension or kinking of vessels
  • Micro suture and micro suture penetration injury
  • Disturbances of coagulation
  • Ischemia reperfusion injury

The role of routine post-operative anticoagulation in microsurgery has been debated for years but has not defined conclusively. Anti-coagulation can increase the chance of hematoma both at the flap donor and recipient sites, and even in rare circumstances, may cause an allergic reaction. However, familiarity and personal experience play a large role in post-operative anti-coagulation regimens from surgeon to surgeon. Anti-coagulation is felt by some to reduce the chance of post-operative clotting at the anastomosis site. Most commonly, aspirin and dextran are used. Intravenous heparin is generally utilized when difficulty is encountered, such as post-operative thrombosis. The most commonly used pharmacological agents are:

  1. Aspirin
  2. Dextran
  3. Heparin
  4. Leeches

Each is used to block a specific site in the clotting cascade to inhibit thrombosis. In addition, leeches also act mechanically to remove stagnant blood and bring in new oxygenated flow.

Aspirin

Aspirin is an inhibitor of both prostaglandin synthesis and platelet aggregation.

Aspirin affects platelet aggregation by irreversibly inhibiting prostaglandin cyclo-oxygenase. This effect lasts for the life of the platelet and prevents the formation of the platelet aggregating factor thromboxane A2. At somewhat higher doses, aspirin reversibly inhibits the formation of prostaglandin I2 (prostacyclin), which is an arterial vasodilator and inhibitor of platelet aggregation.

At higher doses aspirin is an effective anti-inflammatory agent, partially due to inhibition of inflammatory mediators via cyclo-oxygenase inhibition in peripheral tissues. In vitro studies suggest that other mediators of inflammation may also be suppressed by aspirin administration, although the precise mechanism of action has not been elucidated. It is this non-specific suppression of cyclo-oxygenase activity in peripheral tissues following large doses that leads to its primary side effect of gastric irritation.

Aspirin is usually given at does of 80 to 325 mg daily. In pediatric microsurgery, aspirin use needs to be considered carefully because of the association of Reye's Syndrome with aspirin in children.

Dextran

Dextrans are macromolecules composed of glucose subunits. They are given intravenously (IV) and have a number of beneficial effects in health care. They were originally designed as volume expanders to treat hypovolemia or shock because they are both osmotically active, and too large to pass through the uninjured vessel wall.

Dextran has numerous pharmacological effects when infused intravenously:

  • Anti-platelet activity
  • Anti-fibrin activity
  • Plasma volume expansion in hypovolemia
  • Improves micro circulation by decreasing blood viscosity and impeding erythrocyte aggregation

Microsurgeons use dextran because it binds to platelets, red blood cells, and the lining of the vessel wall. This decreases the ability of platelets to stick together and ultimately form clots. When the endothelium is injured, elements normally covered become exposed. This activates circulating platelets which adhere to the vessel wall and each other, starting a cascade which results in occlusion or clotting of the vessel lumen. Endothelium will heal and return to a "non-stick" state after about 5 days. Dextran is used to protect vessel patency for this period of time.

Dextran 40 is usually given at a dose of 25 milliliters per hour for approximately 5 days post-operatively after microvascular transplantation. In children, dextran 40 is usually run at 8-10 milliliters/kg/24hours. 

Complications are rare with dextran use.

Heparin

Heparin is a glycosaminoglycan that is a naturally produced substance. It has an anticoagulation effect by inhibiting the formation of fibrin clots. Heparin acts primarily at the following sites in the normal coagulation system:

  • Combines with anti-thrombin III (heparin cofactor) to accelerate the neutralization of thrombin which prevents conversion of fibrinogen to fibrin
  • Inactivates factor X which prevent conversion of pro thrombin to thrombin
  • Prevents the formation of a stable fibrin clot by inhibiting the activation of fibrin-stabilizing factor.

Heparin does not have fibrinolytic activity, therefore it will not lyse existing clots.

The dose of heparin is dependent on multiple factors. In microsurgery, clinical response is often the end point, rather than results of diagnostic tests of anticoagulation.

Leeches

Leeches secrete a powerful anticoagulant - hirudin - that can be used in clinical medicine. Leeches are applied to venous congested flaps or replanted fingers to relieve congestion and vasodilate the micro circulation. This results in bleeding of the leech bite site for several hours after the leech has filled its intestines and stopped working. Hirudin inhibits thrombin and is secreted by the leeches into the flap or finger. The continuous oozing of blood that results from leech application to the replanted part or congested flap allows inflow and outflow of blood to continue until neovascularization occurs. After neovascularization, blood can then drain via newly formed capillaries.

A Working Leech

A leech working to decompress a congested finger tip. The oozing of blood from the leech site after the leech is satiated can continue for several hours. Dressings become saturated with blood and need frequent changes.

Leeches are raised under strict conditions and stored in a large tank, ready to spring into action if needed. In our institution, the pharmacy stores and cares for them.

Since leeches are colonized with Aeromonas hydrophila, a bacterium that can cause soft tissue infection, prophylactic antibiotics are begun at the initiation of leech therapy. Typical antibiotic prophylaxis is cefotaxime or ciprofloxacin.

Leeching can result in significant blood loss over time, so blood counts need to be done at least frequently. The possibility of blood transfusion increases with leech therapy.

Bibliography

  1. Buntic RF, Brooks D. Standardized protocol for artery-only fingertip replantation. J Hand Surg Am. 2010 Sep;35(9):1491-6.
  2. Buncke GM, Buntic RF, Romeo O. Pediatric mutilating hand injuries. Hand Clin. 2003 Feb;19(1):121-31.
  3. Buntic RF, Brooks D, Buncke HJ, Buncke GM.Dextran-related complications in head and neck microsurgery: do the benefits outweigh the risks? Plast Reconstr Surg. 2004 Sep 15;114(4):1008.
  4. Buncke. HJ. Microsurgery: Transplantation and Replantation. Lea and Fiebinger, Philadelphia. 1991.