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Anticoagulation Therapy
in Microsurgery: A Review
Morad Askari, MD, Christine Fisher, BS, Frederick G. Weniger, MD,
Sean Bidic, MD, W. P. Andrew Lee, MD
From the Division of Plastic and Reconstructive Surgery, University of Southern California, Los Angeles, CA;and the Division of Plastic and Reconstructive Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA. The advent of microsurgical tissue transfer including replantation greatly has expanded the
scope of reconstructive surgery. There are few recent innovations in anticoagulation therapies
for microsurgery, however, and anastomotic thrombosis remains an occasional cause of
surgical failure. No consensus exists on the ideal anticoagulation protocol for microsurgery.
This article reviews major pharmacologic modalities of anticoagulation, delineates the
mechanism of action and study of efficacy of each agent, and compares the risks and benefits
of popular anticoagulation therapies. Finally, it examines available human outcomes– based
data and attempts to provide a glimpse of the future direction of microsurgical anticoagula-
tion research. (J Hand Surg 2006;31A:836 – 846. Copyright 2006 by the American Society
for Surgery of the Hand.)
Key words: Microsurgery, anticoagulation, thrombosis, flap, heparin.
Microvascular techniques are key compo- microsurgicalanticoagulationhasyettobeidenti- fied or whether no singular effective method ex- correct various congenital, ablative, and traumatic defects. Hand surgeons use microsurgi- This article reviews selected literature relating to cal procedures to replant amputated digits or repair anticoagulation for microsurgery and provides a injured nerves and blood vessels. Intraoperative or summary of relevant basic science and clinical stud- postoperative anastomotic thrombosis necessitates ies in animal and human models. We hope that this re-operation and risks flap or replant failure. Sur- review will assist surgeons with informed decision gical intervention for thrombosis generally in- making regarding the clinical use of anticoagulants in volves anastomotic revision or interposition vein grafting. Despite these interventions vascular Overview of Thrombosis in Microsurgery
thrombosis is the leading cause of failure of mi- The pathogenesis of venous thrombosis differs from reported to be as high as 10%, the primary preven- derlying cause of arterial thrombosis whereas venous tion of thrombosis is of critical interest to micro- thrombosis is primarily the result of fibrin Because venous thrombosis occurs more frequently Although anticoagulation has been part of re- than arterial thrombosis as the cause of free flap constructive surgery for 30 years, anticoagulation failure, fibrin strand development is a more signifi- protocols vary widely among microsurgeons. Cur- cant factor in microvascular occlusion than platelet rently 96% of reconstructive surgeons use antico- The risk for thromboses is highest (80%) during ies evaluating prophylactic anticoagulation in the first 2 postoperative days and decreases to 10% microsurgery report efficacy in animal models, after postoperative day In a study of the timing however, limited human data exist to support any of pedicle thrombosis Ichinose et found that 90% clinician’s preferred method. It is unknown of purely arterial thrombi occur on postoperative day whether the most efficacious protocol for human 1 whereas 42% of purely venous thrombi occur after Askari et al / Anticoagulation in Microsurgery postoperative day 1. This risk pattern is attributed to currently the anticoagulant agent used most widely the initially low flow volume through the pedicle, by surgeons to prevent both arterial and venous which gradually increases in the postoperative period.
Several surgical factors are associated with free enhances its antiprotease activity and accelerates its flap failure. The use of vein grafts in microsurgery attachment to its substrate approximately 1,000-fold.
and the presence of chronic wounds at recipient sites As a result the active forms of coagulation factors II are associated with greater postoperative vascular (thrombin), IX, X, XI, and XII are rendered inactive and vein grafts are associated with increased throm- hibition of thrombin generation heparin reduces the bosis at the site of anastomosis and the free rectus activation of coagulation factors V and VIII, recruit- abdominis and transverse rectus abdominis muscle flaps are associated with increased patency compared antithrombotic effect of heparin is measured clini- cally by the increase in clotting time of blood and is Despite the variety of reconstructive techniques expressed as prolonged activated partial thrombo- and anticoagulation protocols used by microsur- plastin time (APTT). A 2-fold increase in PTT is geons, the reported failure rate among free flaps considered a therapeutic heparin level. In addition, ranges from 4% to 10% and the reported failure rate large doses of heparin result in vasodilation that possibly is mediated by the release of nitric oxide Many flaps are salvaged successfully with thrombo- lytic treatment, indicating that the true rate of vascu- heparin may reduce thrombosis further by increasing lar thrombosis in microsurgery is Optimal prophylactic anticoagulation therapy promises signif- Heparin prophylaxis is limited by an increased risk for hemorrhage from the surgical site and formationof Heparin therapy is associated with a Antithrombotic Therapy
greater incidence of hematoma than aspirin or dex- The use of prophylactic antithrombotic agents is the tran. In a retrospective study of lower-extremity re- most common strategy for avoiding vascular throm- construction using free flaps Pugh et found a bosis after free flap surgery or vascular 66% rate of hematoma formation when heparin was used alone or in combination with other agents. This crease patency rates of microvascular repairs sur- warrants discretion when administering unfraction- geons need agents that (1) decrease platelet function ated heparin because increased tissue pressures (eg, aspirin), (2) increase blood flow or decrease caused by the formation of a hematoma at the site of blood viscosity (eg, dextran), and (3) counteract the anastomosis can compromise perfusion and encour- effects of thrombin on platelets and fibrinogen (eg, age thrombogenesis. In a recent retrospective review heparin). Today aspirin, dextran, and heparin are the of 216 head and neck reconstruction patients given a mainstay of treatment. The use of these agents re- combination of aspirin (325 mg every day) and sub- mains complicated by the challenge of providing cutaneous heparin (5,000 U subcutaneously twice a optimal antithrombotic prophylaxis while minimiz- day), Chien et reported a free-flap survival rate equivalent to other anticoagulation regimens without No consensus exists on the use of anticoagulation therapy after microsurgery. Many surgeons have Another important side effect of heparin therapy is their own particular protocols for perioperative anti- coagulation that has been shaped by personal trials I HIT is a rare (1%–3%) immune-mediated condition and errors. The following sections review and sum- that results in a significant decrease in platelet count marize experimental studies and clinical experiences (30,000 –55,000) 5 to 10 days after the initiation of reported in the current literature and provide an over- heparin therapy. It is treated only by cessation of view and comparison of popular anticoagulation heparin therapy. Type II HIT is a nonimmune con- dition with a smaller decrease in platelet count(100,000), which occurs 1 to 2 days after the initia- tion of heparin therapy. Type II HIT usually im- Heparin, a polyglycosaminoglycan of varying lengths, proves spontaneously despite continuation of heparin has been used clinically for more than 50 years. It is The Journal of Hand Surgery / Vol. 31A No. 5 May–June 2006 in hypotension in patients having cardiac surgery or occurrence of hematoma and hemorrhage in compar- clude its low bioavailability and unpredictable dose- Topical heparin irrigation may increase vessel pa- tency but the direct effect of the pressure can injure to postoperative patients necessitates close monitor- the vessel. Yan et areported that in the animal ing of fluctuating coagulation levels, which extends model lactated Ringer’s solution pressures of 100 the length and increases the cost of the hospital mm Hg or greater injures the endothelial cells and internal elastic lamina, which may have a detrimental The goal in heparin therapy is the efficient delivery effect on microvascular anastomoses. Therefore irri- of a minimal therapeutic dose to the site of vascular gation pressures less than 100 mm Hg minimize anastomosis. Maintaining low systemic heparin lev- trauma to the delicate microvascular tissues and max- els minimizes the adverse effects of anticoagulation.
Rooks et reported no significant difference in theprotective effect of intra-arterial and systemically administered intravenous heparin or dextran-40. In Low molecular weight heparin (LMWH) is a deriv- other studies systemic heparin provided greater pro- ative of unfractionated heparin that is prepared tection against rethrombosis after the repair of a through the deaminative hydrolysis of standard hep- thrombosed anastomosis by vein graft repair than by arin into short polysaccharide fragments. These mol- simple re-anastomosis alone (82% vs 69% patency, ecules are known to have the same inhibitory effect on active factor X but have a weaker antithrombin arin, when administered systemically to a therapeutic (factor II) activity. As a result LMWH is as effica- level (a 2-fold increase in PTT), reduces the rate of cious as unfractionated heparin in preventing venous primary venous thrombosis by 60% whereas higher doses result in close to a 100% reduction. Higher et alobserved that LMWH (dalteparin) thrombin plasma levels of heparin result in better protection inhibition is sufficient to prevent thrombosis and against vascular thrombosis but increase the inci- does not cause a significant increase in bleeding. By using a rat model of deep arterial injury, doses of 180 local doses of heparin while maintaining low sys- U/kg LMWH or heparin caused a similar antithrom- temic levels, Hudson et used an in situ venous botic effect (close to 3-fold increase in patency at 30 catheter. The catheter was inserted proximal to the minutes after surgery) but only the heparin group re- venous anastomosis in 83 free flaps to infuse 50 sulted in a statistically significant increase in bleeding.
U/mL at 10 mL/h for 48 hours and then the dose was The efficacy of LMWH to prevent arterial throm- tapered over 5 days. They observed an increase of bosis is a point of debate. Although some studies local APTT whereas the systemic APTT remained clearly have found LMWH to be a less effective normal. Ultimately they reported zero re-explora- treatment than traditional heparin in reducing the tions or flap failures in comparison with the usual re-exploration rate of 12% in the absence of local ported better or equal results.In a rabbit model Zhang et observed a 50% increase in the patency Recently topical antithrombotic administration has of arterial anastomoses with LMWH in comparison been suggested as an alternate approach to local with no anticoagulation, but observed no difference anticoagulation.Fu et alreported that topical in the patency of small venous anastomoses.
administration of high-concentration heparin (750 ␮g/ The side-effect profile of LMWH is superior to mL) results in 80% patency at the anastomosis sites unfractionated heparin. In addition to causing fewer at 7 days in the rabbit model. Ten minutes of intra- hematomas LMWH has higher bioavailability (85% operative irrigation with high-dose heparin directly compared with 10%), a longer plasma half-life, a on the anastomosis optimizes endothelial binding of the drug and increases the local concentration of fewer cases of thrombocytopenia compared with un- clinical study, however, Khouri et did not ob- reliable anticoagulation over a longer period of time serve a benefit to using intraluminal heparin irriga- tion, regardless of concentration, in reducing postop- LMWH can be administered on an outpatient basis, erative thrombosis. They did report a decrease in the which reduces the length of hospitalization time.
Askari et al / Anticoagulation in Microsurgery Low molecular weight heparin has a lesser effect enteroides streptococcus These agents are used com- on APTT than does unfractionated heparin. This monly by microsurgeons to decrease vascular throm- value was found to be 3-fold lower for the lowest bosis. The antithrombotic effect of dextran is dose of dalteparin with distinct antithrombotic effect mediated through its binding to erythrocytes, plate- (180 U/kg) compared with the same dose of unfrac- lets, and vascular endothelium, increasing their elec- tionated Therefore the level of activity of tronegativity and thus reducing erythrocyte aggrega- LMWH is expressed best as units of anti–activated tion and platelet adhesiveness. Dextrans decrease factor X (factor Xa) activity instead of In a platelet adhesion by decreasing factor VIII-Ag (von rat model Ritter et alshowed that a single injection Willebrand’s factor). Platelets coated in dextran are of either unfractionated heparin or LMWH just be- distributed more evenly in a thrombus and are bound fore pedicle division results in a similar anastomotic by coarser fibrin, which simplifies thrombolysis. By patency and flap survival rate. Both increased APTT inhibiting ␣-2 antiplasmin, dextran also serves as a and anti–factor Xa levels but LMWH had a more prominent increase on anti–factor Xa, less of an dextrans that remain in blood vessels act as potent increase in APTT, and no bleeding complications compared with unfractionated heparin. In addition expansion causes hemodilution, which improves the protective effects of LMWH include antithrom- blood flow and further increases patency of micro- bin-independent effects such as the release of tissue anastomoses. No difference has been observed in the factor pathway inhibitor, interactions with heparin antithrombotic efficacy of intra-arterial versus intra- cofactor II, and platelet factor Therefore attempts to standardize LMWHs on the basis of anti-Xa activity The varying size of dextran, from 10 to 150 kd, have not been completely successful. This explains the results in prolonged antithrombotic and colloidal ef- inherent difficulty in determining equivalent doses of fects.Larger dextrans are excreted poorly from the unfractionated heparin to LMWHs. The pharmaco- kidney and remain in the blood for weeks until they logic profiles and efficacies of LMWHs vary; there- fore success with one LMWH at a certain dose does kd) is the most popular dextran for anticoagulation.
Close to 70% of Dextran-40 is excreted in the urine Similar to unfractionated heparin the application within the first 24 hours after intravenous infusion of topical LMWH minimizes systemic side effects.
and the remaining 30% is retained for several more Chen et examined the effects of topical heparin and topical LMWH (enoxaparin) on the patency of Although there are relatively few side effects as- anastomosed vessels. The thrombosis rate for the first sociated with dextran use, they can be very serious.
7 days was reduced significantly after either treat- These include anaphylaxis, volume overload, pulmo- ment in comparison with saline irrigation. They did nary edema, cerebral edema, or platelet dysfunc- not find a statistical difference in patency or bleeding dextran’s osmotic effect is acute renal A doses (2 mg/kg) of subcutaneous LMWH (enoxaparin) direct toxic effect on the tubules and glomeruli or were most effective at dilating capillaries (by 33%) intraluminal hyperviscosity are 2 proposed mecha- without bleeding complications in an animal Patients with a history of diabetes melli- Ertas et reported significant capillary dilation in tus, renal insufficiency, or vascular disorders are at rat cremaster muscle 5 hours after administration of 2 greatest risk. Brooks et alrecommended avoiding mg/kg and 4 mg/kg LMWH. The efficacy of higher dextran therapy in patients with chronic renal insuf- LMWH doses (8 mg/kg) was no different than con- ficiency and a creatinine clearance rate of less than trol, but caused markedly increased bleeding. Lower 40 mL/min. In a prospective randomized comparison doses of LMWH increase functional capillary perfu- of dextran- and aspirin-related complications in 100 sion at the microcirculatory level of a rat cremaster patients undergoing microsurgical flap reconstruction muscle flap without increased propensity for bleed- for head and neck malignancy, aspirin and dextran ing in the predissection and postdissection period.
were equally efficacious in preventing flap failure.
Patients on dextran, however, had a 3.9- to 7.2-fold increased relative risk of systemic complications af- Dextrans are a group of variously sized polysaccharides ter 48 and 120 hours of dextran infusion, respec- that are synthesized from sucrose by Leuconostoc mes- tively. Because the benefits of dextran prophylaxis The Journal of Hand Surgery / Vol. 31A No. 5 May–June 2006 do not outweigh the risks, dextran is a less commonly thrombus formation at both arterial and venous mi- croanastomoses and results in better microcirculationthrough the muscle flap. Low-dose aspirin is pre- ferred by many surgeons because it does not affect Reconstructive surgeons frequently use aspirin (ace- endothelial and smooth muscle cyclooxygenase. As a tylsalicylic acid [ASA]) in the perioperative period to result prostaglandin I (platelet antagonist and vasodi- improve flap survival. Aspirin acetylates and inhibits lator) production is unaffected and there are fewer sys- the platelet enzyme cyclooxygenase, impeding ara- chidonic acid breakdown to thromboxane and pros- The same mechanisms that make aspirin a power- tacyclin. Thromboxane is a potent vasoconstrictor ful antithrombotic tool also can cause major prob- that induces platelet aggregation and prostacyclin is a lems. Platelet dysfunction results in increased blood vasodilator that inhibits platelet aggregation. There is loss during surgery, which increases transfusion and evidence that aspirin impairs thrombin generation re-operation Experimentally desmopressin is and reactions catalyzed by this enzyme at the site of helpful to reduce thrombus formation and increase overall platelet function after aspirin Other rin is known to prevent microvascular thrombosis at aspirin side effects stem from its nonselective inhi- both anastomoses sites, although it is less effective bition of cyclooxygenase. Cyclooxygenase-I has been referred to as the housekeeping enzyme because venous heparin yields higher patency compared with it is expressed in many normal tissues in the body enterically delivered aspirin. Assessment with a and regulates functions such as blood flow to the scanning electron microscope proved that more fibrin kidney and protection of gastric By affect- accumulates in aspirin-treated vessels and more ing the gastric mucosa and reducing platelet aggre- platelets aggregate in a heparin-treated gation aspirin can cause serious gastrointestinal The timing of aspirin administration relative to the bleeding. This risk is dose dependent and a low-dose time of surgery alters efficacy. Kort et did not regimen (75 mg/d) minimizes the risk for find any protective effect of aspirin administered 30 Newer cyclooxygenase-II–selective inhibitors are as- minutes before surgery in rats. Similarly periopera- sociated with fewer renal and gastric side effects but tive administration of oral aspirin at 30 mg/kg in a rat do not prevent platelet aggregation, therefore they do thrombosis model did not provide antithrombotic protection at 24 The administration of aspi-rin (4 mg/kg) 10 hours before surgery resulted in a significant increase in patency and decreased the rate Thrombolytic agents available for clinical use in- clude streptokinase, urokinase, and tissue-type plas- of ASA given before surgery resulted in a 2-fold minogen activator. Their efficacy in reversing micro- increase in vessel patency at 1 week after anastomo- vascular thrombosis is well documented in the sis compared with control. Another study measured the protective effect of systemic aspirin (adminis- scant. In a retrospective multi-institutional study Yii tered orally) in the maintenance of rat vein graft et reported no significant improvement in pa- patency when administered for 1 week before sur- tency with the use of thrombolytic therapy in free- flap salvage; however, Rooks et reported that for The protective effect of aspirin doubles when co- an established thrombus, urokinase results in marked administered during surgery with another antiplatelet improvement in patency compared with heparin and dextran. They reported an advantage to intra-arterial ASA with dipyridamole results in better venous pa- over intravenous administration of thrombolytics be- tency than heparin alone (40% compared with 6.7%) cause intra-arterially delivered urokinase results in and provides less arterial protection (6.7% compared significantly greater efficacy (100% for intra-arterial with 73.3%) 1 day after surgery. The combination of vs 40% intravenous). Because most human studies the 3 provides the best arterial and venous antithrom- look at small study populations there are no definitive botic In their search for the ideal aspirin conclusions on the relative efficacy and appropriate dose Peter et found that low-dose aspirin (5 dosing of thrombolytics; however, it is known that mg/kg, infused intra-arterially immediately after ar- flap salvage is most successful on the first postoper- terial and venous anastomosis in a rat model) reduces ative day compared with postoperative day 2 and Askari et al / Anticoagulation in Microsurgery a risk for bleeding but this risk can be minimized by ron Corp., Emeryville, CA) is more effective than draining the venous effluent to prevent systemic ex- heparin when added to irrigation solution used on thrombus-prone rabbit In a multicenter,multinational, blinded, randomized, phase II study Khouri et found that intraluminal irrigation with Medical scientists continue to search for new anti- low concentrations of SC-59735 (0.05 mg/mL) re- thrombotic and anticoagulant therapies that maxi- sulted in a flap failure rate similar to treatment with mize benefits while minimizing adverse effects. The either high-dose SC-59735 (0.15 mg/mL) or heparin efficacy of these agents was tested primarily in the (100 U/mL). Irrigation with low-dose SC-59735, cardiovascular setting and only recently are these however, resulted in a marked incidence of hema- agents being investigated in microsurgery.
toma formation compared with high-dose SC-59735 Hemorrheologic agents such as pentoxifylline or heparin. Thus they suggested that a lower dose of (PTX) (Trental; Hoechst-Roussel Pharmaceutical, recombinant human TFPI improves flap survival Inc., Somerville, NJ) typically are used to treat while minimizing the formation of postoperative he- chronic occlusive arterial disease. They augment blood flow by vasodilating vessels, inhibiting platelet Studies of Iloprost (CoTherix Inc., San Francisco, aggregation, and reducing fibrinogen levels. In addi- CA) report almost twice the rate of patency after tion PTX decreases blood viscosity by increasing resection, repair, and re-anastomosis of thrombosed erythrocyte deformability, which improves tissue significant when vein grafts were used. Illoprost, in improved microcirculation and oxygenation in however, is less effective than systemic heparin at various Because PTX requires a 2-week win- maintaining patency at sites of vein graft re-anasto- dow before the drug is effective, a 2-week preoper- ative regimen is necessary. In a randomized blinded study to determine the efficacy of thromboprophy- ment with ibuprofen and indomethacin markedly im- lactic LMWH and pentoxifylline in the rat microvas- proved micrograft patency in a carotid rat model with cular free groin flap model, Murthy et reported a no significant difference when compared with aspi- statistically significant improvement in arterial pa- rin. Similarly the use of toradol (ketorolac) has been tency with both LMWH and pentoxifylline, but not in combination. Inconsistent and insufficient human perioperative oral ticlopidine, a known platelet inhib- data make the prophylactic use of PTX in microsurgery itor, has been shown to be more effective at main- taining patency at both 1 hour and 1 week in a rabbit Recently recombinant hirudin, a compound origi- model in comparison with aspirin (45% and 15% nally isolated from medicinal leeches, has been used patency rates at 1 hour and 1 week, respectively, for as an anticoagulant. A specific thrombin inhibitor, ticlopidine compared with 35% and 10%, respec- hirudin is more potent than heparin without adversely tively, for The greatest increase in patency compared with control at 1 week occurred when spaces inside microthrombi because it does not re- aspirin and ticlopidine were administered concur- quire a cofactor, and therefore is smaller (7,000 d) rently, as opposed to when either agent was given than the bulky heparin–antithrombin III individually (20% patency at 1 week).
Similar to heparin, however, hirudin can cause sig-nificant bleeding when administered Clinical Studies
Fu et reported that a high concentration of top- Despite refined microsurgical skills and antithrom- ical recombinant hirudin (750 ␮g/mL) results in sig- botic therapeutic options, 6% to 25% of microsurgi- nificantly increased patency at 7 days (75% com- cal cases result in re-operation because of thrombosis pared with 13.3% in the control group) with minimal bleeding in a rabbit microanastomosis model.
has been performed primarily in animal models.
Tissue factor pathway inhibitor (TFPI), a naturally Some researchers have suggested that the rodent occurring protein, blocks the tissue factor pathway of model has a uniquely higher rate of recanalization in coagulation. It forms complexes with tissue factor thrombosed veins, which calls for caution in extrap- VIIa and Xa, thus inhibiting the coagulation cas- olating rodent data to human problems. There is a The Journal of Hand Surgery / Vol. 31A No. 5 May–June 2006 paucity of data in the literature comparing anticoag- of anticoagulation. One criticism of the study is that ulation options in human microsurgery. Therefore each surgeon used the anticoagulation protocol with current recommendations for microsurgical anticoag- which he or she was accustomed. Therefore each ulation therapy are based on extrapolations of con- surgeon used an anticoagulation regimen appropriate flicting animal data and scant human studies.
to his or her specific technique. This confounding Recent literature examines the current state of the factor may invalidate conclusions drawn from this art in anticoagulation for microsurgery. A 2001 arti- cle by Conrad and reviewed the actions of Although no data clearly support any specific an- dextran, aspirin, and heparin and recommended an- ticoagulant for microsurgery, this review provides a ticoagulation regimens for free flaps and replants.
summary of current data to assist the clinician in They recommended preoperative and postoperative designing a rational approach to anticoagulation for chewed aspirin daily for 2 weeks, intraoperative hep- microsurgery. The timing of anticoagulation, route of arinized saline irrigant, and a heparin bolus of 50 to anticoagulation, the use of combination therapy, and 100 U/kg before releasing the clamps. For replants individualization of microsurgical anticoagulation to the surgical technique may improve future microsur- at 0.4 mL/kg/h, weaned off by postoperative day 5.
The appropriate timing of anticoagulation therapy use of an indwelling axillary catheter to deliver mar- maximizes its effectiveness. The first 2 days after caine for 5 days to produce a chemical sympathec- surgery are crucial in anticoagulation because the tomy, the use of chlorpromazine as a peripheral va- majority of clots form during this time. The best time sodilator and sedative for 3 to 5 days, and the use of to initiate anticoagulation treatment, however, may 325-mg aspirin for 3 weeks. His recommendations not necessarily be on those days. In their prospective were not based on specific animal studies and were outcomes study of free-flap surgeries, Khouri et al not the results of large outcomes studies of different reported a 2-fold decrease in flap failure (this was not methods of anticoagulation for microsurgery.
statistically significant) with preoperative use of as- The only human study to look at this issue recently pirin, dextran, or heparin. A significant antithrom- was the previously discussed study by Khouri et botic effect is observed after a single dose of aspirin This was a 6-month prospective study of 23 surgeons who performed 493 free flaps. This study looked at tion is not popular secondary to an increased risk for many variables and provided associations between intraoperative bleeding and most surgeons are in- different methods of anticoagulation and flap failure clined to initiate anticoagulation after the procedure.
rates. Khouri et alreported that only subcutaneous Khouri et alconcluded that the postoperative use of heparin significantly differs in its clinical effect, as subcutaneous heparin is superior to any other peri- subcutaneous heparin decreased the odds ratio for operative administration. Similarly the route of anti- thrombosis by 27%. No other antithrombotic regi- coagulant delivery is a subject of interest. The effects men had a statistically significant association with of local delivery may differ from the systemic deliv- Another part of the solution may lie not in choos- not statistically significant. There was flap failure in ing the right antithrombotic therapy but in finding the 2.2% of patients who were given preoperative sys- best combination of agents. In the conclusion of their temic therapy such as heparin, aspirin, or dextran.
study Peter et alsuggested using systemic low-dose Patients without preoperative systemic therapy expe- aspirin with heparin locally for irrigation of mi- rienced 4.6% flap failure. In addition, patients who crovessels to maximize antithrombotic effect while received intraoperative systemic heparin as a part of minimizing side effects. Indeed future research may a normal prophylactic anticoagulation protocol had a best be directed toward a combination of popularly 5.6% flap failure rate versus 2.9% when no heparin used therapies rather than comparing single agents was used in the normal protocol. There were no associations with outcomes reported for patients who The lack of progress in understanding how best to received dextran, aspirin, or heparinized intraopera- anticoagulate microsurgical patients may stem from the oversimplified attempt to apply a one-size-fits-all ap- It should be noted that Khouri’s was not proach to microsurgical patients. A review of the di- designed specifically to compare different methods verse anticoagulation protocols used in various study Askari et al / Anticoagulation in Microsurgery models and of the inconsistent outcomes reported for Corresponding author: W. P. Andrew Lee, MD, Division of Plastic similar treatments indicates a need for individualized Surgery, University of Pittsburgh School of Medicine, 3550 Terrace St,Scaife Hall, Suite 690, Pittsburgh, PA 15261; e-mail:
anticoagulation therapy. In an effort to elucidate indi- Copyright 2006 by the American Society for Surgery of the Hand vidual risk Olsson et alinvestigated coagulation and fibrinolysis during various microsurgical tissue trans- fers and found an association between specific plasma References
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Bibliography Kilpisjärvi If you like to receive a copy of any of the following reprints, please mark theappropriate number and return the list to the address above. - Suomalaisen Eläin- ja Kasvitieteellisen Seuran VanamonLinden, J. 1943. Bidrag till kännedomen om vegetation ochEnontekis lappmarks björk- och fjällregioner. biologisestamerkityksestä. - Luonnontutkija 1: 1-5. Kalela,


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