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Leech Therapy - Anticoagulation Protocols

last modified on: Mon, 11/25/2019 - 10:49

Medicinal Leech Therapy on Head and Neck Patients

return to: Microvascular Surgery Protocols; see Free Flap Monitoring and Salvage
 

Theory Behind Using Leeches


Venous congestion occurs when the veins that drain blood from a tissue are unable to do their job because of clotted blood within them or from external pressure on the draining vein. Blood then accumulates in the tissue as it cannot get out. This accumulated blood eventually can destroy the integrity of the tissue and the tissue can die. Venous congestion in the majority of cases is best managed by returning the patient rapidly to the OR to remove the venous obstruction. In rare situations, this is not possible or not indicated, and in these situations leeches may be used to alleviate the venous congestion.

Leeches produce an enzyme in their saliva called hirudin. Hirudin is a powerful anticoagulant. They produce this to prevent their host from forming a clot so that they can feast on blood more easily. When you apply a leech, the hirudin acts locally at the bite site to allow continued bleeding for 2-3 hours after the leech is removed. While attached, the leech actively removes some of the built up blood which eases the pressure within the tissue. After the leech is removed, the built up venous blood will continue to drain from the site where the leech was attached, which is therapeutic for the tissue. The effects of the hirudin may last up to a few hours. You can tell that it's no longer active when the blood stops draining. It is at that time that you should apply another leech, unless directed by the physicians to do otherwise.

In most instances, you need only apply one or two leeches at a time. Then, when you apply the next leech, you place it in a different spot on the tissue area that needs to be treated. Sometimes, if we're dealing with a very large flap, we will instruct you to use more than one leech. Always, if you have any questions about how many leeches to use or where to place them, call us at any time.

When you apply a leech, you have to herd it away from areas where you don't want it to attach. Applying a small amount of D5 to the desired area will encourage the leech to begin feeding. When it finds a spot that it's happy with, it will latch on. Then, when it's full, it will let go and wander off. Actively feeding leeches should never be pulled off. It is at the critical moment when the leech releases that the nurse has to catch the leech and euthanize it, or it might wander off and get lost, or worse, decide that it wants to reattach somewhere else...like the patient's eye or mouth. It is the responsibility of the patient's nurse to prevent this complication from happening, and we realize that this is a very labor intensive treatment.

All patients undergoing leech therapy need to be receiving a fluroquinolone (we typically use Levaquin), which should be started before the 1st leech is applied and continued until 24 hours after leech therapy is discontinued. If there are any open or necrotic wounds on the treated area, the antibiotic should be continued until they are closed. That is because leeches carry many bacteria in their saliva (most common of which is Aeromonas hydrophila) which may cause wound infections. If your patient is not on Levaquin, please address this issue with the OTO resident. If Levaquin is discontinued too early, please alert us to that as well.

Directions For Handling Medicinal Leeches

  1. Leeches are ordered from pharmacy.
  2. Leeches are to be applied to the tissue that we want to treat. In most cases, this would be the skin of the inset free flap. However, this may be any skin that looks dusky after a surgery, even if it's not a free flap. The OTO resident should "outline" with plastic drapes the area in which leeches are to be applied. The plastic drapes can be arranged to help "contain" the leeches within the area of concern.
  3. Patient is started on Levaquin.
  4. Ask the resident how many leeches are to be used per session. (Usually it's just one, maybe two.)
  5. Ask the resident if you have any doubts about where the leech should be applied.
  6. Place the leech on this tissue. It will wiggle around a bit looking for a good spot. If it starts to leave the area that we want to treat, use your gloved hands as a wall to force it to stay in the right area. Placing a small amount of D5 on the desired area will encourage the leech to begin feeding.
  7. When it stops wiggling, it's probably attached. Never squeeze an attached leech; it may vomit the Aeromonas that lives in its stomach which would increase the chance of wound infection.
  8. Examine the leech frequently (every 10 minutes or so) to make sure that it's still in place. You can expect the leech to stay in place for at least 30 minutes.
  9. When the leech lets go, pick it up and place it in a jar of 95% ethanol. This will euthanize it. It is to be returned to pharmacy.
  10. You will see that the site where the leech was attached will ooze dark (venous) blood. Place moist gauze over it to absorb the blood. Wipe this spot every 15 minutes or so to see if fresh blood is still oozing. When it stops oozing, apply another leech.
  11. Don't be surprised if the orders change a little, such as "apply leech q 2 H" as opposed to waiting for the draining to stop.
  12. Serial hematocrits, q8 hours, should be obtained on patients undergoing leech therapy. It is not unusual for repeated transfusions to be required in patients undergoing leech therapy.

 Free flap anticoagulation protocols

 

Argatroban

Mechanism of action: Argatroban is a synthetic direct thrombin inhibitor that reversibly binds to the thrombin active site. Its anticoagulant effects are achieved by inhibiting thrombin-catalyzed or -induced reactions, including fibrin formation; activation of coagulation factors V, VIII, and XIII; activation of protein C; and platelet aggregation.

Application: Used for patients who require systemic anticoagulation when there is a diagnosis of heparin-induced thrombocytopenia. Administered as an IV infusion with or without bolus dose. Following are guidelines for argatroban administration when used for treatment of HIT, which may be used for patients needing systemic anticoagulation during free flap procedures. There are other guidelines for argatroban use for treatment of major vessel thrombosis which prescribe higher doses.

  1. Obtain baseline aPTT.
  2. Start infusion at 2 mcg/kg/minute. Follow aPTT every 2 hours, with goal aPTT 1.5 - 3 times baseline.
  3. Increase or decrease by 1 mcg/kg/minute based on aPTT.
  4. There is no guidance on duration of therapy in this setting.

Pharmacodynamics: Immediately upon initiation of Argatroban infusion, anticoagulant effects are produced as plasma Argatroban concentrations begin to rise. Steady-state levels of both drug and anticoagulant effect are typically attained within 1 to 3 hours and are maintained until the infusion is discontinued or the dosage adjusted. Steady-state plasma Argatroban concentrations increase proportionally with dose (for infusion doses up to 40 mcg/kg/min in healthy subjects), which correlates with increases of the activated partial thromboplastin time (aPTT). Although other global clot-based tests including prothrombin time (PT), the International Normalized Ratio (INR), and thrombin time (TT) are affected by Argatroban, the therapeutic ranges for these tests have not been identified for Argatroban therapy.

Precautions: Argatroban undergoes hepatic clearance, and doses should be modified in the setting of hepatic dysfunction. Pregnancy Category B.

References: Argatroban Injection package insert. Research Triangle Park, NC: GlaxoSmithKline; 2005.

tPA (Alteplase)

 *Off-label use

tPA, or Alteplase, is a thrombolytic agent whose use has been described in the salvage of free flaps in several studies, including Rinker et al. Its role is in the setting of venous anastomotic failure resulting in thrombosis of the vasculature of the flap. Urokinase has also been described in this role (D'Arpa et al., Serletti et al.). Alteplase binds to fibrin in a thrombus and converts the entrapped plasminogen to plasmin, thereby initiating fibrinolysis. It is indicated for catheter dysfunction due to thrombus formation. Half-life is 5 minutes, and clearance is primarily by the liver. Contraindication is known hypersensitivity; Pregnancy class C.

  1. Take down venous anastomosis so tPA is not introduced systemically.
  2. Load Alteplase into a TB syringe with short 27g needle
  3. Initial tPA (Alteplase) dose is 2mg, which is perfused through the flap through the arterial side, either through the opened anastomosis or through a side branch.
  4. Repeat once if needed
  5. Consider systemic anticoagulation as well

References

  • Rinker BD, Stewart DH, Pu LL, Vasconez HC. Role of recombinant tissue plasminogen activator in free flap salvage. J Reconstr Microsurg. 2007 Feb;23(2):69-73.
  • D'Arpa S, Cordova A, Moschella F. Pharmacological thrombolysis: one more weapon for free-flap salvage. Microsurgery. 2005;25(6):477-80.
  • Serletti JM, Moran SL, Orlando GS, O'Connor T, Herrera HR. Urokinase protocol for free-flap salvage following prolonged venous thrombosis. Plast Reconstr Surg. 1998 Nov;102(6):1947-53.

 

Counteracting anticoagulants and antiplatelet agents

Medication

Mechanism

Intervention

Comments

Anticoagulants

 

 

 

Warfarin

Inhibits Vitamin K as cofactor in production of Factors II, VII, IX, X

Effect begins 4-6 hours after administration and takes 24 hours to lower the INR. Infers resistance to subsequent warfarin effect for 1 week.

Heparin (IV bolus or infusion; no treatment for SQ heparin)

Heparin-antithrombin complex inhibits thrombin and Xa; may also reduce platelet aggregation

Protamine, 1 mg per 100U heparin given if bolus was < 1 hour before or infusion stopped <3 hours before

  • May also use DDAVP
  • HIT thrombocytopenia starts day 7-14. When antibodies are present (~100 days), platelet transfusion may increase arterial thrombosis

Low molecular weight heparin (Lovenox, Fragmin)

Inhibition of Xa

Protamine, 1 mg per mg Lovenox given in last 4 hours

 

Antiplatelet agents

 

 

 

Aspirin

Irreversibly blocks COX, preventing formation of TXA2

  • Platelet transfusion
  • DDAVP

 

ADP-receptor blockers (Plavix, Ticlid)

Irreversible noncompetitive inhibition of ADP surface binding site

  • Platelet transfusion
  • DDAVP

 

Glycoprotein receptor (GPIIb/IIIa) blocking agents (Reopro, Integrilin, Aggrastat)

Interfere with platelet surface receptor binding of fibrinogen

  • Reopro- platelet transfusion
  • Integrilin or Aggrastat- platelets and fibrinogen

Normal platelet function resumes 48 hours after withholding Reopro, and 4-8 hours after holding Integrilin or Aggrastst

Fibrinolytics
(Activase, streptokinase, urokinase, Retavase, TNKase)

Attach to fibrin or accelerate plasminogen pathway

Cryoprecipitate, 10 units

 

Thrombin inhibitors
(argatroban, Refludan, Angiomax)

 

No direct reversal agents

May use DDAVP, plasma concentrate of vWF, and rFVIIa

 

 

DDVAP – desmopressin, 0.3 mg/kg. Increases release of factor VIII and vWF, thereby improving platelet adhesion

FFP – fresh frozen plasma, 20 ml/kg IV. Repeat if continuing hemorrhages
Platelets – 5 units

rFVIIa – recombinant factor VIIa, 20-90µg/kg. May be useful for reversing anticoagulant and antiplatelet drugs, but is “off-label” use

COX – cyclo-oxygenase

HIT – heparin induced thrombocytopenia

TXA2 – thromboxane A2

vWF – von Willibrand factor


References

Powner DJ, Hartwell EA, Hoots WK. Countering the effects of anticoagulants and antiplatelet agents during neurosurgical emergencies. Neurosurgery. 2005 Nov; 57(5):823-31.