Regional Anesthesia Anticoagulation

By: Honorio T. Benzon, MD & Rasha S. Jabri, MD

 

Table of contents

I. INTRODUCTION

II. ANTIPLATELET THERAPY

III. ORAL ANTICOAGULANTS

IV. HEPARIN

  • Intravenous Heparin
  • Subcutaneous Heparin
  • Low-Molecular-Weight Heparin

V. THROMBOLYTIC THERAPY

  • Thrombin Inhibitors
  • Fondaparinux

VI. HERBAL THERAPY

VII. CLINICAL FEATURES, DIAGNOSIS, &MANAGEMENT OF EPIDURAL HEMATOMA

VIII. SUMMARY COMMENTS ON ANTICOAGULANTS & NEURAXIAL BLOCKS

IX. ANTICOAGULATION & PERIPHERAL NERVE BLOCKS

X. REFERENCES

Introduction

Intraspinal hematoma is a relatively rare condition resulting froma variety of causes. Its incidence is approximately 0.1 per 100,000 patients per year.1,2 Traumatic causes include lumbar puncture and neuraxial anesthesia aswell as a complication of spinal surgery. It is more likely to occur in anticoagulated or thrombocytopenic patients, patients with neoplastic disease, or in those with liver disease or alcoholism.3,4 Spontaneous bleeding is rare but may be seen from spinal an arteriovenous malformation or vertebral hemangioma. Approximately one quarter to one third of all cases are associated with anticoagulation therapy.5,6

Hemorrhage into the spinal canal commonly occurs in the epidural space because of the presence of a prominent epidural plexus of veins. Puncture of epidural vessels during placement of epidural catheters occurs in approximately 3–12% of cases. The incidence of symptomatic epidural hematoma associated with epidural analgesia is difficult to estimate, but combined case series of more than 100,000 epidural anesthetics have been reported without a single epidural hematoma. Spinal hematoma is a rare but devastating event. The actual incidence of neurologic dysfunction resulting from hemorrhagic complications associated with neuraxial blockade is unknown; the incidence cited in the literature is estimated to be 1 in 150,000 epidural and 1 in 220,000 spinal anesthetics. However, the incidence increased significantly after the introduction of low-molecular-weight heparin (LMWH), before the Food and Drug Administration issued a warning, and before the American Society of Regional Anesthesia (ASRA) issued its initial consensus statement in 1998.7

The risk of formation of intraspinal hematoma after administration of neuraxial anesthesia and analgesia is increased in patients who received anticoagulant therapy or have a coagulation disorder.8 For that reason neuraxial anesthesia is often contraindicated in the presence of a coagulopathy. Other risk factors for development of epidural or spinal hematoma include technical difficulty (multiple attempts) in the performance of the neuraxial procedures due to anatomic abnormalities of the spine and multiple or bloody punctures. Intraspinal hematoma is more often associated with epidural catheter use than with the other neuraxial block techniques.

ASRA has recommended guidelines for the safer performance of neuraxial blocks in patients who are on anticoagulants.7,9 These guidelines were based on extensive review of the literature and of the pharmacology of the different anticoagulants. Recommendations were made on the timing of the neuraxial block and removal of the epidural catheter and the administration of the anticoagulants. In particular, the use of low concentrations of local anesthetics for epidural infusion (preservation of motor strength for easier monitoring) and subsequent neurologic monitoring were recommended by ASRA. The initial consensus guidelines, published in 1998 and updated in 2003 [7,9], greatly assisted clinicians in decision making with regard to the use of neuraxial procedures in the setting of anticoagulation therapy and possibly decreased the incidence of epidural and spinal hematoma. In this chapter, we discuss the significance of common antiplatelet, anticoagulation, and fibrinolytic therapy and hope to offer the reader a guide in decision making about the use of neuraxial anesthesia and PNBs in clinical practice.
Antiplatelet therapy

Antiplatelet medications, including aspirin, nonsteroidal antiinflammatory drugs (NSAIDs), and dipyridamole, have been in the past considered relative contraindications to central neural blockade by some authors due to prolongation of the bleeding time and a theoretically greater risk of formation of spinal hematoma. Antiplatelet medications inhibit the platelet cyclooxygenase enzyme and prevent the synthesis of thromboxane A2. Thromboxane A2 is a potent vasoconstrictor and facilitates secondary platelet aggregation and release reactions. Platelets from patients on these medications have normal platelet adherence to subendothelium and normal primary hemostatic plug formation. An adequate, although potentially fragile, clot may form.10 However, although such plugs may be satisfactory hemostatic barriers for smaller vascular lesions, they may not ensure adequate perioperative hemostatic clot formation. The role of platelets in coagulation and hemostasis is shown in Figures 1 and 2.

Figure 1. Role of platelets in coagulation. Platelets carry out their role in hemostasis through three basic reactions: adhesion, activation (and secretion), and aggregation. When the blood vessels are stripped of endothelium, platelets rapidly bind to the subendothelium by a process termed adhesion.
Figure 2. Role of platelets in coagulation. Another important task of the platelet is to support plasma coagulation reactions.When activated, platelets bind several important plasma protein complexes. They secrete an activated form of factor V (factor Va), which binds to the platelet surface and binds factor Xa. Platelet-bound factor Xa then markedly accelerates the conversion of prothrombin to thrombin.

The Ivy bleeding time was considered to be a reliable predictor of abnormal bleeding in patients receiving antiplatelet drugs.11 However, the postaspirin bleeding time is not a reliable indicator of platelet function.12,13 There is large intra- and interpatient variability in the results of the test. Although the bleeding time may normalize within 3 days after aspirin ingestion, platelet function as measured by platelet response to adenosine diphosphate (ADP), epinephrine, and collagen may take up to aweek to return to normal. There is no evidence to suggest that bleeding time can predict hemostatic function, and studies failed to show a correlation between aspirin-induced prolongation of the bleeding time and surgical blood loss.1,14 Therefore, measurement of an Ivy bleeding time before induction of spinal or epidural anesthesia may not identify those patients at increased risk for hemorrhagic complications. Other NSAIDs (naproxen, piroxicam, ibuprofen) produce only a short-term, mild defect that normalizes within 3 days.15 Platelet function in patients receiving antiplatelet medications should be assumed to be decreased for 1 week with aspirin and 1–3 days with NSAIDs. This assumption does not take into consideration the continuous formation of new, functional platelets. This continuous production of fresh, normally functioning platelets, combined with the residual function of already circulating platelets may explain the relative safety of performing neuraxial procedures in these patients.

Special platelet function assays are now available to monitor platelet aggregation and degranulation. The platelet function analyzer (PFA) is a test of in vitro platelet function. It is a good screening test for vonWillebrand disease and monitors the effect of desmopressin administration. The PFA is prolonged after antiplatelet therapy.16,17 The test simulates the process of platelet adhesion and aggregation by measuring the ability of platelets to occlude a microscopic aperture in a membrane coated with collagen and epinephrine (C-EPI) or collagen and ADP (C-ADP) under controlled high shear rates. The time required to obtain a complete platelet plug is the closure time in seconds. The normal closure times are 60–160 sec for C-EPI and 50–124 sec forC-ADP.The intake of aspirin and NSAIDs prolongs the closure time of C-EPI, but von Willebrand disease, low platelet count (<100,000/UL), lowhematocrit (<30%), and renal failure prolong the closure time for C-ADP.

Possible clinical significance of antiplatelet therapy and the risk of epidural and spinal hematoma in patients on antiplatelet therapy has been raised by a case report of spontaneous epidural hematoma formation in the absence of spinal or epidural anesthesia in a patient with a history of aspirin ingestion.18 The patient developed severe lower extremity weakness after ingestion of 1500 mg of aspirin in the form of an aspirin-containing antacid. A myelogram revealed intraspinal hematoma and neurologic defect at the T5 to T6 level. The cerebrospinal fluid was clear, although prolonged bleeding from the lumbar puncture site was noted after myelography. A laminectomy was performed, and the intraspinal hematoma was removed. The patient’s neurologic function gradually improved. Nevertheless, the risk associated with the administration of spinal or epidural anesthesia to a patient receiving antiplatelet medications remains very controversial. Although Vandermeulen and colleagues implicated antiplatelet therapy in 3 of the 61 cases of spinal hematoma occurring after spinal or epidural anesthesia.19 Several large studies have demonstrated the relative safety of central neural blockade in combination with antiplatelet therapy. The Collaborative Low-dose Aspirin Study in Pregnancy (CLASP) Group [20] included 1422 high-risk obstetric patients who were administered 60 mg of aspirin daily and underwent epidural anesthesia without any neurologic sequelae. However, no data regarding difficulty of the procedure or bleeding during the placement or removal of the epidural needle or catheter was noted.20 In a retrospective study of 1013 spinal and epidural anesthetics in which antiplatelet drugs were taken by 39% of the patients including 11% of patients who were on multiple antiplatelet medications, no patient developed signs of spinal hematoma; however, patients on antiplatelet medications showed a higher incidence of blood aspiration throughthe spinal or epidural needle or the catheter.21 In a subsequent prospective study in 1000 patients, 39% of which reported preoperative antiplatelet therapy, there were no hemorrhagic complications.22 Blood was noted during needle or catheter placement in 22% of patients, and there was frank blood in 7% of the patients. Therefore, preoperative antiplatelet therapy was not a risk factor for bloody needle or catheter placement. Female gender, increased age, history of excessive bruising or bleeding, continuous catheter technique, large needle gauge, multiple attempts, and difficult needle placement were noted to be significant risk factors. Clinical studies in pain clinic patients are similar to those undergoing surgery. Patients on aspirin[10] or NSAIDs[23] who underwent epidural steroid injections did not develop signs and symptoms of intraspinal hematoma.

The lack of correlation between antiplatelet medications and bloody needle or catheter placement provides strong evidence that preoperative antiplatelet therapy does not represent a significant risk factor for the development of neurologic dysfunction from spinal hematoma in patients on antiplatelet therapy. Although there have been case reports of intraspinal hematoma in patients on aspirin and NSAIDs, there were complicating factors in these case reports.24 These included concomitant heparin administration,[25] coexisting epidural venous angioma[25] and technical difficulty in performing the procedure.26–28 Technical difficulties in performing the injection have been identified as major risk factors in the development of intraspinal hematoma after neuraxial injections.

Based on the available evidence, ASRA made several recommendations concerning antiplatelet medications.9,29 Preoperative antiplatelet therapy does not represent a significant risk factor for the development of neurologic dysfunction from spinal hematoma in patients on antiplatelet therapy. There is no wholly accepted test, including the bleeding time, to guide antiplatelet therapy. Careful preoperative assessment of the patient is important in identifying conditions that might lead to increased risk of bleeding. The timing of intake of the NSAIDs does not represent a specific concern in relation to the placement of single-shot spinal or catheter techniques, postoperative monitoring, or the timing of neuraxial catheter removal. The risk of bleeding complications, however, may be increased in patients on several antiplatelet medications and concurrent use of other medications affecting clotting mechanisms, such as oral anticoagulants, standard heparin, and low-molecular-weight heparin (LMWH).9,29

Cyclooxygenase-2 (COX-2) inhibitors gained popularity because of their analgesic properties and lack of platelet and gastrointestinal effects. Studies showed their perioperative analgesic property in a variety of perioperative settings.30–33 The drugs have minimal gastrointestinal toxicity and are ideal for patients who are at increased risk for serious upper GI adverse events. Compared with aspirin or NSAIDS, the effects of the COX-2 inhibitors on platelet aggregation and bleeding times were not different from a placebo.34–36 Blood loss did not increase during spinal fusion surgery when COX-2 inhibitors were given preoperatively.37 The platelet properties of these drugs make them ideal for perioperative use when neuraxial anesthetic is planned. Unfortunately, rofecoxib and valdecoxib have been withdrawn from the market because of their cardiovascular side effects;[38] only celecoxib is presently being used, but at dosages lower than previously recommended.

Clinical Pearls
  • Preoperative antiplatelet therapy does not represent a significant risk factor for the development of neurologic dysfunction from spinal hematoma in patients on antiplatelet therapy.
  • There is no wholly accepted test, including the bleeding time, to guide antiplatelet therapy.
  • Careful preoperative assessment of the patient is important in identifying conditions thatmight lead to increased risk of bleeding.
  • The timing of intake of the NSAIDs does not represent a specific concern in relation to the placement of single shot spinal or catheter techniques, postoperative monitoring, or the timing of neuraxial catheter removal.
  • The risk of bleeding complications may be increased in patients on several antiplatelet medications and concurrent use of other medications affecting clotting mechanisms, such as oral anticoagulants, standard heparin, and low-molecular-weight heparin.
  • COX-2 inhibitors have minimal gastrointestinal toxicity and are ideal for patients who are at increased risk for serious upper GI adverse events. Compared with aspirin or NSAIDS, the effects of the COX-2 inhibitors on platelet aggregation and bleeding times were not different from a placebo.
  • It is recommended that clopidogrel (Plavix) be discontinued for 10 to 14 days before a neuraxial injection.

The thienopyridine drugs ticlopidine and clopidogrel have no direct effect on arachidonic acid metabolism. These drugs prevent platelet aggregation by inhibiting adenosine diphosphate (ADP) receptor-mediated platelet activation.39,40 They also modulate vascular smooth muscle reducing vascular contraction. Clopidogrel was noted to be 40–100 times more potent than ticlopidine.41 Clinical doses are usually 75 mg daily for clopidogrel and 250 mg twice a day for ticlopidine. Ticlopidine is rarely used at the present time because it causes neutropenia, thrombocytopenic purpura, and hypercholesterolemia. Clopidogrel is preferred because of its improved safety profile and proven efficacy. It was found to be better than aspirin in patients with peripheral vascular disease.42 The maximal inhibition of ADP-induced platelet aggregation with clopidogrel occurs 3–5 days after initiation of a standard dose (75 mg), but within 4 to 6 hafter the administration of a large loading dose of 300 to 600 mg.43 The large loading dose is usually given to patients before they undergo percutaneous coronary intervention.40,44 There has been a case report of spinal hematoma in a patient on ticlopidine.45 Although there has been no case of intraspinal hematoma in a patient on clopidogrel alone, a case of quadriplegia in a patient on clopidogrel, diclofenac, and aspirin has been reported.46

As stated, ASRA concluded that neuraxial blocks may be performed in patients on aspirin, NSAIDs or COX-2 inhibitors.9,29 For the thienopyridine drugs, it is recommended that clopidogrel be discontinued for 7 days and ticlopidine for 10 to 14 days before administration of a neuraxial injection. The longer interval for ticlopidine is due to the increase in its half-life with chronic administration, its half-life increases from 12 h after a single dose to 4 to 5 days after a steady state is reached.
Oral Anticoagulants

Warfarin exerts its anticoagulant effect by interferingwith the synthesis of the vitamin K-dependent clotting factors (VII, IX, X, and thrombin)[47–49] (Figure 3).

Figure 3. Vitamin K-dependent coagulation factor synthesis. Vitamin K is necessary for posttranslational modification of prothrombin, proteins C and S, and factors VII, IX, and X. Vitamin K is stored in hepatocytes.

It also inhibits the anticoagulants protein C and S. Factor VII has a relatively short half-life (6–8 h) and the prothrombin time (PT) may be prolonged into the therapeutic range (1.5–2 times normal) within 24 to 36 h. The anticoagulant protein C also has a short half-life (6–7 h). The initial prolongation of the international normalized ratio (INR) is therefore the result of competing effects of reduced factor VII and protein C and the washout of existing clotting factors.

Because of this, the INR is unpredictable during the initial stage of treatment with warfarin.50,51 Factor VII participates only in the extrinsic pathway, and adequate anticoagulation is not achieved until the levels of biologically active factors II (half- life of 50 h) and X are sufficiently depressed. This requires 4–6 days. High loading doses of warfarin (15–30 mg) are occasionally employed for the first 2–3 days of therapy, and the desired anticoagulant effect is achieved within 48 to 72 h.52 The anticoagulant effect of warfarin persists for 4 to 6 days after termination of therapy while new biologically active vitamin K factors are synthesized. The effect of warfarin can be reversed by the transfusion of fresh frozen plasma and vitamin K injections. The risks of warfarin usage are bleeding and the rare occurrence of skin necrosis. Its drawbacks also include the necessity of monitoring its effect with serial monitoring of INR, its interaction with other drugs, and the fact that it has to be discontinued a few days before surgery.47,48 Few data exist regarding the risk of spinal hematoma in patients with indwelling spinal or epidural catheters who are subsequently anticoagulated with warfarin. Odoom and Sih[53] performed 1000 continuous lumbar epidural anesthetics in 950 patients who underwent vascular procedures and received preoperative oral anticoagulant. The thrombotest (a test measuring factor IX activity) was decreased and the activated partial thromboplastin time (aPTT) was prolonged in all the patients prior to the epidural placement. Heparin was also administered intraoperatively. The epidural catheters remained in place for 48 h postoperatively, the coagulation status of the patients at the time of catheter removal was not described. There were no neurologic complications. Although the results of this study are reassuring, the obsolescence of the thrombotest as a measure of anticoagulation combined with the unknown coagulation status of the patients at the time of catheter removal limits the usefulness of the study.

The use of an indwelling epidural or intrathecal catheter and the timing of its removal in an anticoagulated patient is controversial. Although the trauma of needle placement occurs with both single-dose and continuous catheter techniques, the presence of an indwelling catheter could provoke additional injury to tissues and vascular structures. No spinal hematomas were reported in 192 patients receiving postoperative epidural analgesia in conjunction with low-dose warfarin after total knee arthroplasty.54 In this study, the patients received warfarin to prolong their prothrombin times (PTs) to 15.0 to 17.3 sec. The epidural catheters were left indwelling for 37 ± 15 h (range 13–96 h). The mean PT at the time of epidural catheter removal was 13.4 ± 2 s (range 10.6– 25.8 sec). This and several subsequent studies documented the relative safety of low-dose warfarin anticoagulation in patients with an indwelling epidural catheter.51,55 However, patients varied greatly in their response to warfarin, and the authors recommended close monitoring of coagulation status to avoid excessive prolongation of the PT. Since intraspinal hematomas have occurred after removal of the catheter,[19] it is recommended that the same laboratory values apply to placement and removal of the epidural catheter.56 Factors responsible for a prolonged PT and PTT are illustrated in Figures 70–4 through 70–6.

Figure 4. Coagulation reaction: Factors responsible
for a prolonged (PTT) are in the shaded area. Patients who have an abnormal PTT but whose PT and other tests are normal can be divided in two groups: those who are prone to bleeding and those that are not. The
patients who do not bleed may have an extremely prolonged PTT (90 seconds or more) but do not have history of bleeding. They will have deficiency in factor XII, prekalikrein, or high-molecular weight kininogen. These patients should not be denied surgery or epidural anesthesia. The other group, patients who bleed, have both prolonged PTT and a history of bleeding. They will have a deficiency of factor VII (hemophilia A), factor IX (hemophilia B or Christmas disease) or factor XI.
Figure 5. Coagulation reaction: Factors involved in prothrombin time (PT) are in the shaded area. The prothrombin time is carried out by adding a source of tissue factor to the patient’s plasma along with calcium or phospholipid. Tissue factor forms a complex with and activates factor VII. (Ca = calcium; PL = phospholipid.)
Figure 6. Coagulation reaction: Factors involved in partial thromboplastin time (PTT) are in shaded area. In assessing the PTT, coagulation is initiated by an agent that activates the Hageman factor– kininogen–prekalikrein complex. Most coagulation factors are screened by PTT, except factors VII and XIII, the protein that stabilizes fibrin clots by cross-linking them, as well as components of the fibrinolytic system. (Ca = calcium; PL = phospholipid.)

The ASRA recommended an INR value of 1.4 or less as acceptable for the performance of neuraxial blocks.9,48 The value was based on studies that showed excellent perioperative hemostasis when the INR value was ≤ 1.5.49 Studies on the levels of clotting factors at different INR values showed that the decline of these factors may not be significant at an INR of 1.5. At INR values of 1.5 to 2.0, the concentrations of factor II were noted to be 74% to 82% of baseline, whereas factor VII levels were 27% to 54% of baseline values.50 At INR values of 2.1 ± 1 during the initial phase of warfarin administration, factors II and VII were 65 ± 28% and 25 ± 20% of control values.57 Levels of 20% of normal are considered adequate for normal hemostasis at the time of major surgery. Another study[58] found that at INRs of 1.3 to 2, under stable anticoagulation with warfarin, the concentrations of the clotting factors VII, IX, and X were within normal limits.

The clinician should be aware of the interactions of warfarin on the coagulation cascade and the role of the INR in monitoring its effect. To minimize the risk of complications, ASRA recommended several precautions.9,48 Chronic oral therapy should be stopped and the INR measured before a neuraxial block is performed. The concurrent use of other medications, such as aspirin, NSAIDs, and heparins, that affect the clotting mechanism increases the risk of bleeding complications without affecting the INR. If an initial dose of warfarin is given prior to surgery, the INR should be checked if the dose was given more than 24 h earlier. If patients are on low-dose warfarin treatment (mean daily dose approximately 5 mg) during epidural analgesia, the INR should be checked daily and before catheter removal if the initial dose was given more than 36 h previously. Higher daily doses may need more intensive monitoring. The warfarin dose should be held or reduced when the INR is > 3 in patients with indwelling neuraxial catheters to prevent epidural hematoma and hemarthroma. While on warfarin therapy, the patient’s neurologic status should be checked routinely during epidural analgesic infusion, aswell as 24 h after the catheter has been removed. Dilute concentrations of local anesthetic should be utilized to minimize the degree of sensory and motor blockade. Clinical judgmentmust be exercised in making decisions about removing or maintaining neuraxial catheters in patients with therapeutic levels of anticoagulation during neuraxial catheter infusion. The warfarin dose should be reduced for patients who are likely to have an enhanced response to the drug, especially the elderly. For patients on chronic oral anticoagulation, the warfarin must be stopped and the INR measured.

Clinical Pearls
  • Chronic oral therapy with warfarin should be stopped and the INR measured before a neuraxial block is performed.
  • The concurrent use of othermedications, such as aspirin, NSAIDs, and heparins, that affect the clotting mechanism increases the risk of bleeding complications without affecting the INR.
  • If an initial dose of warfarin is given prior to surgery, the INR should be checked if the dose was given more than 24 h earlier.
  • In patients on low-dose warfarin treatment (mean daily dose approximately 5 mg) during epidural analgesia, the INR should be checked daily and before catheter removal if the initial dose was given more than 36 h previously. Higher daily doses may need more intensive monitoring.
  • The warfarin dose should be held or reduced when the INR is > 3 in patients with indwelling neuraxial catheters to prevent epidural hematoma and hemarthroma.
  • While on warfarin therapy, the patient’s neurologic status should be checked routinely during epidural analgesic infusion, as well as 24 h after the catheter has been removed. Dilute concentrations of local anesthetic should be utilized to minimize the degree of sensory and motor blockade.
  • Clinical judgment must be exercised in making decisions about removing or maintaining neuraxial catheters in patients with therapeutic levels of anticoagulation during neuraxial catheter infusion. The warfarin dose should be reduced for patients who are likely to have an enhanced response to the drug, especially the elderly.
Heparin

Intravenous Heparin

Heparin is a complex polysaccharide that exerts its anticoagulant effectby binding to antithrombin III. The conformational change in antithrombin accelerates its ability to inactivate thrombin, factor Xa, and factor IXa.59

In addition, unfractionated heparin releases a tissue factor pathway inhibitor from endothelium, enhancing its activity against factor Xa.60 The anticoagulant effect of heparin increases disproportionately with increasing dosages. The anticoagulant effect of subcutaneous heparin takes 1–2 h, but the effect of intravenous heparin is immediate. In fact, the coagulation time is prolonged two to four times the baseline level 5 min after the intravenous injection of 10,000 units of heparin. Heparin has a half-life is 1.5–2 h. It should be noted that patients with acute thromboembolic disease clear heparin more rapidly.Within 4 to 6 h of its administration, the therapeutic dose of heparin ceases. The aPTT is used to monitor the effect of heparin; therapeutic anticoagulation is achieved with a prolongation of the aPTT to greater than 1.5 times the baseline value or a heparin level of 0.2 to 0.4 U/mL.61 The aPTT is usually not prolonged by the subcutaneous administration of lowdoses heparin and is not monitored. Protamine neutralizes the effect of intravenously administered heparin.

Heparin is not the ideal anticoagulant since it is a mixture of molecules only a fraction of which has anticoagulant activity. It binds to platelet factor 4 and to the von Willebrand factor.62,63 The heparin–antithrombin complex is also not very effective in neutralizing clot-bound thrombin. Finally, heparin is associated with immunologic thrombocytopenia and immune-mediated thrombosis.62 For patients receiving standard heparin therapy, the risk of bleeding complications is increased in the presence of other medications that affect other clotting mechanisms, including aspirin, NSAIDs, LMWH, and oral anticoagulants.

Several studies demonstrated the safety of spinal or epidural anesthesia followed by systemic heparinization if certain precautions are observed. Rao and El-Etr[64] reported no spinal hematomas in over 4000 patients who underwent lower extremity vascular surgery under continuous spinal or epidural anesthesia. In their study, patients with preexisting coagulation disorders were excluded, heparinization occurred at least 60 min after catheter placement, the level of anticoagulation was carefully monitored, and the indwelling catheters were removed at a time when heparin activity was low. Surgery was canceled in patients when frank blood was noted in the needle and performed the following day under general anesthesia. The same findings were noted in a subsequent report in the neurologic literature. Ruff and Dougherty[65] noted spinal hematomas in 7 of 342 (2%) patients who underwent lumbar puncture and subsequent heparinization for evaluation of cerebral ischemia. The presence of blood during the procedure, concomitant aspirin therapy, and heparinization within 1 where identified as risk factors in the development of spinal hematoma.

Clinical Pearls

PATIENTS ON HEPARIN THERAPY

  • There should be at least a 1-h delay between neuraxial needle placement and heparin administration.
  • The epidural catheter should be removed 2–4 h after the last heparin dose and 1 h before subsequent heparin administration.
  • Partial thromboplastin time (PTT) or activated coagulation time (ACT) should be monitored to avoid excessive heparin effect.
  • Dilute concentrations of local anesthetics are recommended to minimize motor blockade; the patient should be followed postoperatively for early detection of reoccurrence of motor blockade.
  • In the event of a traumatic (bloody) or difficult needle placement, there are no data to support mandatory cancellation of surgery.

NEURAXIAL ANALGESIA IN PATIENTS UNDERGOING CARDIOPULMONARY BYPASS

  • Neuraxial procedures should be avoided in patients with known coagulopathy.
  • Surgery should be delayed 24 h in the patient with a traumatic (bloody) tap.
  • The time from the neuraxial procedure to the systemic heparinization should exceed 1 h.
  • Heparinization and reversal should be monitored and closely controlled.
  • The epidural catheter should be removed when normal coagulation is restored.
  • Patients should be monitored closely for signs of spinal hematoma.

ASRA made several recommendations when a neuraxial technique is used in the presence of intraoperative anticoagulation.9,66 The technique should be avoided in patients with other coagulopathies. There should be at least a 1-h delay between needle placement and heparin administration. The catheter should be removed 2–4 h after the last heparin dose and 1 h before subsequent heparin administration. The PTT or ACT should be monitored to avoid excessive heparin effect. The patient is followed postoperatively for early detection of reoccurrence of motor blockade. Dilute concentrations of local anesthetics are recommended to minimize motor blockade. Although there may be an increased risk in the event of a traumatic (bloody) or difficult needle placement, there are no data to support mandatory cancellation of surgery. The decision to proceed should be based on appropriate clinical judgment and full discussion with the surgeon and the patient.

Neuraxial procedures are occasionally performed in patients who undergo cardiopulmonary bypass. The following precautions have been recommended to prevent the development of intraspinal hematoma[67]:

  1. Neuraxial procedures should be avoided in patients with known coagulopathy.
  2. Surgery should be delayed 24 h in the patient with a traumatic tap.
  3. The time from the neuraxial procedure to the systemic heparinization should exceed 1 h.
  4. Heparinization and reversal should be monitored and controlled tightly.
  5. The epidural catheter should be removedwhen normal coagulation is restored. and the patient should be monitored closely for signs of spinal hematoma.

Subcutaneous Heparin

The therapeutic basis of low-dose subcutaneous heparin (5000 units every 8–12 h) is heparin-mediated inhibition of activated factor X. Smaller doses of heparin are required when administered as prophylaxis rather than as treatment for thromboembolic disease. Following intramuscular or subcutaneous injection of 5000 units of heparin, maximum anticoagulation effect is observed in 40 to 50 min and returns to baseline within 4 to 6 h. The aPTT may remain in the normal range and often is not monitored. However, wide variations in individual patient responses to subcutaneous heparin have been reported. Neuraxial techniques are not contraindicated during subcutaneous (minidose) prophylaxis, but the risk of bleeding may be reduced by delaying the heparin administration until after the block. Bleeding may be increased in debilitated patients or after prolonged therapy. The safety of major neuraxial anesthesia in the presence of anticoagulation with subcutaneous doses of unfractionated heparin was documented by several publications.66 Although the anticoagulant effect of subcutaneous heparin is less significant than that of intravenous heparin, ideally subcutaneous low-dose heparin should also not be administered within 4 to 6 h of neuraxial anesthesia to allow for normalization of the heparin effect.

Clinical Pearls
  • Neuraxial techniques are not contraindicated in patients receiving subcutaneous (minidose) prophylaxis.
  • Ideally andwhenpractical, the administration of the heparin should be delayed until after spinal or epidural block placement.

 

Low-Molecular-Weight Heparin

Unfractionated heparin is a heterogeneous mixture of polysaccharide chains that can be separated into fragments of various molecular weights.68,69 Each low-molecular-weight heparin (LMWH) fractionation contains heparins of different molecular weights, and each is evaluated as a specific pharmacologic substance. The anticoagulant effect of LMWH is similar to that for unfractionated heparin; it activates antithrombin, accelerating antithrombin’s interaction with thrombin and factor Xa. LMWH also releases tissue factor pathway from the endothelium. LMWH has a greater activity against factor Xa, whereas unfractionated heparin has equivalent activity against thrombin and factor Xa. The plasma half-life of the LMWHs ranges from 2 to 4 h after an intravenous injection and 3–6 h after a subcutaneous injection, its half-life is two to four times that of standard heparin. The longer half-life of LMWH and its dose-independent clearance results in amore predictable anticoagulant response than occurs with heparin. It has a low affinity for plasma protein, resulting in a greater bioavailability. The advantages of LMWH over unfractionated heparin include a higher and more predictable bioavailability after subcutaneous administration and a longer biological half-life. Also, laboratory monitoring the anticoagulant response of LMWH is not measured and dose adjustment for weight is not necessary (although an overdose may occur in smaller patients). LMWH exhibits a dose-dependent antithrombotic effect that is accurately assessed by measuring the anti-Xa activity level. The recovery of anti-factor Xa activity after a subcutaneous injection of LMWH approaches 100%,[70] making laboratory monitoring unnecessary except in patients with renal insufficiency or those with body weight less than 50 kg or more than 80 kg.68 The r time from the thrombelastogram appears to correlate with the serum anti-Xa concentration.71

The three commercially available LMWH in theUnited States are enoxaparin (Lovenox), dalteparin (Fragmin), and tinzaparin (Innohep). Enoxaparin is either given once daily or every 12 h when used as a prophylaxis, and the two other drugs are given once a day. The three drugs appear to have comparable efficacy in the treatment and prevention of venous thromboembolism.72 Enoxaparin and dalteparin have comparable efficacy in the prevention of death ormyocardial infarction among patients with unstable angina.72

Clinical Pearls
  • The anticoagulant effect of LMWH is similar to that for unfractionated heparin; it activates antithrombin, accelerating antithrombin’s interaction with thrombin and factor Xa.
  • The plasma half-life of the LMWHs ranges from 2 to 4 h after an intravenous injection and 3–6 h after a subcutaneous injection, its half-life is two to four times that of standard heparin.
  • LMWHs does not need laboratory monitoring of its anticoagulant response and does need dose adjustment for weight although an overdose may occur in smaller patients
  • Numerous cases of neuraxial hematoma occurred in the United States, prompting the FDA to issue a health advisory in December 1997.

The current recommended thromboprophylactic dose in the United States is 30 mg enoxaparin twice daily. The FDA has recently approved enoxaparin 40 mg once daily, which is similar to the European dosing schedule. It should be noted that patients in Europe get their starting dose 12 h before surgery. Since most patients in the United States are admitted on the day of their surgery, it is not practical for them to get their first dose of LMWH 12 h before surgery. A lot of elderly patients forget to take their medications, and it is not guaranteed that they will take their LMWH at home before their surgery.

Numerous cases of neuraxial hematoma occurred in the United States, prompting the FDA to issue a health advisory in December 1997 and the convening of the first ASRA consensus conference on anticoagulation and neuraxial anesthesia.73 The smallest effective dose of LMWH should be administered. The postoperative administration of LMWH therapy should be delayed as long as possible, with a minimum of 12 h and ideally 24 h postoperatively. A single-dose spinal anesthetic may be the safest neuraxial technique in patients receiving preoperative LMWH. Waiting for at least 12 h after the LMWH prophylactic dose is recommended before performing a spinal technique. Patients who receive higher doses of LMWH (eg, enoxaparin 1 mg/kg twice daily) require longer delays (24 h). The catheter should be removed when anticoagulation activity is low, at least 12 h after prophylactic LMWH administration and 2–4 h before the next dose. Extreme vigilance of the patient’s neurologic status must be observed if LMWH thromboprophylaxis is implemented while an indwelling catheter is infusing. Dilute local anesthetic solution is recommended so that neurologic function can be better monitored. The use of other medications affecting hemostasis, such as antiplatelet drugs, standard heparin, dextran, or oral anticoagulants, in combination with LMWH, creates an additional risk of bleeding complications.

Clinical Pearls

PATIENTS RECEIVING LMWH AND NEURAXIAL ANESTHESIA

  • Monitoring of anti-Xa level is not recommended.
  • The administration other anticoagulant medications with LMWHs may increase the risk of spinal hematoma.
  • The presence of blood during needle placement and catheter placement does not necessitate postponement of surgery. However, the initiation of LMWH therapy should be delayed for 24 h postoperatively.
  • The first dose of LMWH prophylaxis should be given no earlier than 24 h postoperatively and only in the presence of adequate hemostasis.
  • In patients who are on LMWH, needle/catheter placement should be performed at least 12 h after the last prophylactic dose of enoxaparin or 24 h after higher doses of enoxaparin (1 mg/kg every 12 h), 24 h after dalteparin (120 U/kg every 12 h or 200 U/kg every 12 h), and 24 h after tinzaparin (175 U/kg daily).
  • There should be a 12-h interval between the last prophylactic dose of enoxaparin and removal of the epidural catheter. For higher doses of enoxaparin, a 24-h delay is recommended.
  • The LMWH may be administered
Thrombolytic Therapy

Thrombolytic agents actively dissolve fibrin clots that have already formed. Exogenous plasminogen activators such as streptokinase and urokinase not only dissolve thrombus but also affect circulating plasminogen, leading to decreased levels of both plasminogen and fibrin. Recombinant tissue-type plasminogen activator (rt-PA), an endogenous agent, is more fibrin-selective and has less effect on circulating plasminogen levels. Clot lysis leads to elevation of fibrin degradation products, which themselves have ananticoagulant effect by inhibiting platelet aggregation. In addition to the fibrinolytic agent, patients frequently receive intravenous heparin to maintain an aPTT of 1.5 to 2 times normal. Patients with acute myocardial infarction who are treated with thrombolytic therapy (streptokinase or rt-PA) and subsequently heparinized have their fibrinogen and plasminogen levels maximally depressed at 5 h after thrombolytic therapy and remain significantly depressed at 27 h.

Although epidural or spinal needle and catheter placement with subsequent heparinization appears relatively safe, the risk of spinal hematoma in patients who receive thrombolytic therapy is not well defined. Two cases of spinal hematoma in patients with indwelling epidural catheters who received thrombolytic agents have been reported in the literature.74,75 A case of epidural hematoma occurred in a patient with femoral artery occlusion who received an epidural anesthetic for surgical placement of an intraarterial catheter for infusion of urokinase.74 Three hours postoperatively, the patient complained of back pain that progressed to paraplegia despite discontinuation of the urokinase infusion. An emergency decompressive laminectomy was performed, and a large hematoma compressing the thecal sac was evacuated. The patient recovered full neurologic function within 3 days. Another patient with superficial femoral artery occlusion underwent epidural catheter placement for femoral-popliteal artery bypass.75 Blood was noted in the epidural catheter during placement. The patient was given 6300 units of heparin 90 min later, and urokinase was also injected intraarterially during the surgical procedure. A heparin infusion of 1000 u/h was initiated and continued postoperatively for 24 h. The epidural catheter was removed in the recovery room. The patient developed paraplegia on the fourth postoperative day. An MRI revealed an epidural hematoma that extended from T10 through L2. An emergency decompressive laminectomy was performed without improvement in the patient’s neurologic status.

Clinical Pearls
  • Concurrent use of heparin with fibrinolytic and thrombolytic drugs carries a high risk of adverse neuraxial bleeding during spinal or epidural anesthesia.
  • Except in highly unusual circumstances, spinal or epidural anesthesia should be avoided in patients receiving fibrinolytic and thrombolytic therapy.
  • There is no available data to clearly determine the length of time after discontinuation of these drugs and the safe performance of a neuraxial technique.

Fibrinolytic and thrombolytic agents create a coagulation state that poses a unique problem in performing neuraxial anesthesia. There may also be an increased use of these drugs in the perioperative period due to advances in fibrinolytic or thrombolytic therapy, thus requiring increased vigilance. The ASRA guidelines made recommendations with respect to neuraxial procedures after thrombolytic or fibrinolytic therapy.9,76 The concurrent use of heparin with fibrinolytic and thrombolytic drugs places patients at high risk of adverse neuraxial bleeding during spinal or epidural anesthesia. Except in highly unusual circumstances, patients receiving fibrinolytic and thrombolytic therapy should be cautioned against receiving spinal or epidural anesthesia. The time frame for avoidance of these drugs and puncture of noncompressible vessels is 10 days. There is no available data to clearly determine the length of time after discontinuation of these drugs and the safe performance of aneuraxial technique. Frequent neurologic monitoring is recommended for an appropriate length of time in patients who have had neuraxial blocks after fibrinolytic or thrombolytic therapy. If a patient has a continuous epidural infusion and received fibrinolytic or thrombolytic therapy, drugs that minimize sensory and motor blockade should be used. There has been no definitive recommendation on the timing of removal of neuraxial catheters in patients who unexpectedly receive fibrinolytic or thrombolytic therapy. Measurement of fibrinogen levelsmay be helpful in guiding a decision about catheter removal or maintenance.

Thrombin Inhibitors

Recombinant hirudin derivatives, including desirudin, lepirudin, and bivalirudin, inhibit both free and clot-bound thrombin.9 Argatroban, an l-arginine derivative, has a similar mechanism of action. These drugs are primarily used in the treatment of heparin-induced thrombocytopenia. There is no pharmacologic reversal to the effect of these drugs. There have been no case reports of spinal hematoma related to neuraxial anesthesia in patients who have received a thrombin inhibitor. However, spontaneous intracranial bleeding has been reported.9 According to ASRA guidelines, no statement regarding risk assessment and patient management can be made.

Fondaparinux

Fondaparinux is a synthetic anticoagulant that produces its antithrombotic effect through selective inhibition of factor Xa.77 The drug exhibits consistency in its anticoagulant effect since it is chemically synthesized. It is 100% bioavailable. Rapidly absorbed, it reaches maximum concentration within 1.7 h of administration. Its half-life is 17 h.77 Fondaparinux is recommended as an antithrombotic agent following major orthopedic surgery[78] and in the initial treatment of pulmonary embolism.79 The extended half-life (approximately 20 h) allows once-daily dosing. The FDA released fondaparinux with a black box warning similar to that of the LMWHs and heparin.

Clinical Pearls
  • The actual risk of spinal hematoma with fondaparinux is unknown. The daily dosing makes safe catheter removal harder to predict.
  • The use of fondaparinux in the presence of an indwelling epidural catheter is not recommended.

The actual risk of spinal hematoma with fondaparinux is unknown. The daily dosing makes safe catheter removal harder to predict. Both ASRA[9] and the American College of Chest Physicians recommend against the use of fondaparinux in the presence of an indwelling epidural catheter. Their recommendations were based on the sustained and irreversible antithrombotic effect of fondaparinux, early postoperative dosing, and the spinal hematoma reported during the initial clinical trials of the drug. Close monitoring of the literature for risk factors associated with surgical bleeding may be helpful in risk assessment and patient treatment. Performance of neuraxial techniques should occur under conditions used in clinical trials (single needle pass, atraumatic needle placement, avoidance of indwelling neuraxial catheters).9 If this is not feasible, an alternative method of prophylaxis should be considered.

Herbal Therapy
The most commonly used herbal medications are garlic, ginkgo, and ginseng. Garlic inhibits platelet aggregation, and its effect on hemostasis appears to last 7 days. Ginkgo inhibits platelet-activating factor, and its effect lasts 36 h. Ginseng has a variety of effects: it inhibits platelet aggregation in vitro and prolongs both thrombin time and aPPT in laboratory animals, its effect lasts 24 h.9 In spite of their effect on platelet function, herbal drugs by themselves appear to present no added significant risk in the development of spinal hematoma in patients having epidural or spinal anesthesia. Mandatory discontinuation of these medications, or cancellation of surgery in patients in whom these medications have been continued, is not supported by available clinical data. However, the concurrent use of other medications that affect clotting mechanisms, such as oral anticoagulants or heparin, may increase the risk of bleeding complications in these patients. There is no accepted test to assess adequacy of hemostasis in the patient who took herbal medication(s). At this time, there appears to be no specific concerns as to the timing of neuraxial block in relationship to the dosing of herbal therapy, postoperative monitoring, or the timing of neuraxial catheter removal.9
Clinical features, diagnosis & management of epidural hematoma

Patients who develop spinal hematoma usually present with sudden, severe, constant back pain with or without a radicular component. Percussion over the spine aggravates the pain as well as maneuvers that increase intraspinal pressure, including coughing, sneezing, or straining. In addition, the return of the motor weakness and or sensory deficit after the apparent resolution of the epidural or spinal blockade is highly suggestive of epidural or spinal hematoma formation. Motor and sensory findings depend entirely on the level and size of the hematoma, but may include weakness, paresis, loss of bowel or bladder function, and virtually any sensory deficit. MRI is the diagnostic study of choice. The differential diagnosis includes spinal abscess, epidural neoplasm, acute disk herniation, and spinal subarachnoid hemorrhage. Recovery without surgery is rare, andsurgical consultation for consideration of emergent decompressive laminectomy must be obtained. Functional recovery is related primarily to the length of time the symptoms are present, and recovery after 72 h of symptoms is rare. The clinical features, diagnosis and differential diagnosis, and treatment of a patient with a spinal hematoma are discussed in more detail in Chapter 71 (Diagnosis and Management of Intraspinal, Epidural, and Peripheral Nerve Hematoma).

Summary comments on antocoagulations & neuraxial blocks

Anesthesiologists are urged to be up to date on their knowledge of new anticoagulant medications, anticoagulation protocols, and updated guideline recommendations (Table 70–1). Since spinal hematoma may occur even in the absence of identifiable risk factors, vigilance in monitoring is critical for early evaluation of neurologic dysfunction and prompt intervention. The decision to perform neuraxial blockade and the timing of catheter removal in a patient receiving anticoagulant therapy should be made on an individual basis, weighing the benefits of regional anesthesia against the small though definite risk of spinal hematoma.

Table 1: Summary of Guidelines on Anticoagulants and Neuraxial Blocks

I. Antiplatelet medications

  1. Aspirin, NSAIDs, COX-2 inhibitors
    May continue
    Pain clinic patients: Aspirin preferably stopped 2–3 days in thoracic and cervical blocks
    Epidurals (author’s preference—see text)
  2. Thienopyridine derivatives
    a. Clopidogrel (Plavix)—discontinue for 7 days
    b. Ticlopidine (Ticlid)—discontinue for 14 days Do not perform a neuraxial block in patients on more than one antiplatelet drug.
  3. GPIIB/IIIA inhibitors: Time to normal platelet aggregation
    a. Abciximab (Reopro) = 24–48 h
    b. Eptifibatide (Integrilin) = 4–8 h
    c. Tirofiban (Aggrastat) = 4–8 h
    Antiplatelet medications (ASA, Plavix) are usually given after GPIIb/IIIa inhibitors. The above guidelines on aspirin and Plavix should be adhered to.

II. Warfarin

Check INR
INR ≤ 1.5 before neuraxial block or epidural catheter removal

III. Heparin

  1. Subcutaneous heparin (5000 units SQ q 12 h)
    Subcutaneous heparin is not a contraindication against a neuraxial block
    Neuraxial block should preferably be performed before SQ heparin is given
    Risk of decreased platelet count with SG heparin therapy > 5 days
  2. Intravenous heparin
    Neuraxial block: 2–4 h after the last intravenous heparin dose
    Wait ≥ 1 h after neuraxial block before giving intravenous heparin

IV. Low-molecular-weight heparin (LMWH)
No concomitant antiplatelet medication, heparin, or dextran

  1. LMWH Preop
    a. Wait 12 h before a neuraxial block:
    b. Enoxaparin (Lovenox) 0.5 mg/kg bid (prophylactic dose)
    c. Wait 24 h before a neuraxial block:
    d. Enoxaparin (Lovenox), 1 mg/kg bid (therapeutic dose)
    e. Enoxaparin (Lovenox), 1.5 mg/kg qd
    f. Dalteparin (Fragmin), 120 units/kg bid
    g. Dalteparin (Fragmin), 200 units/kg qd
    h. Tinzaparin (Innohep), 175 units/kg qd
  2. LMWH Postop:
    a. LMWH should not be started until after 24 h after surgery
    b. LMWH should not be given until ≥ 2 h after epidural catheter removal
  3. Patients with epidural catheter who are given LMWH
    The catheter should be removed at the earliest opportunity.
    Enoxaparin (0.5 mg/kg): Remove the epidural catheter ≥ 12 h after last dose.
    Enoxaparin (1-1.5 mg/kg), dalteparin, tinzaparin:
    Remove the epidural catheter ≥ 24 h after last dose
    Restart the LMWH ≥ 2 h after the catheter removal
    Summary recommendations for LMWH (preop & postop):
    Wait 24 h except for patients on low-dose enoxaparin (0.5 mg/kg) in which case a 12 h
    interval is adequate.
    Wait 2 h after the catheter is removed before starting LMWH.

V. Specific Xa inhibitor: Fondaparinux (Arixtra)

Short onset, long duration (plasma 1 2 life: 21 h)
ASRA: No definite recommendation
If neuraxial procedure must be performed, recommend single-needle atraumatic placement, avoid indwelling catheter.

VI. Fibrinolytic/Thrombolytic drugs

No data on safety interval for performance of neuraxial procedure
Follow fibrinogen levels
ASRA: No definite recommendation

VII. Thrombin Inhibitors

Desirudin (Revasc)
Lepirudin (Refludan)
Bivalirudin (Angiomax)
Argatroban (Acova)
Anticoagulant effect lasts 3 h
Monitored by aPTT
ASRA: No recommendation at this time because of paucity of data

VIII. Herbal therapy

Mechanism of anticoagulant effect and time to normal hemostasis:
Garlic: Inhibits platelet aggregation, increased fibrinolysis; 7 days
Ginko: Inhibits platelet-activating factor; 36 h
Ginseng: Increased PT and PTT; 24 h
ASRA: Neuraxial block not contraindicated for single herbal medication use
No data on combined herbal therapy

Note: The guidelines are the same for the placement and removal of epidural catheters.
NSAIDs = nonsteroidal antiinflammatory drugs; COX-Z = cyclooxygenese-Z; ASA = acetyl salicylic acid (aspirin); GPIIb = glycoprotein IIb receptor; INR = internationalized ratio, SQ = subcutaneous; LMWH = low-molecular-weight heparin; aPTT = activated partial thrompoplastin time; ASRA = American Society for Regional Anesthesiology; PT = prothrombin time; PTT = partial thromboplastin time.

Reprinted, with permission, from Benzon HT: Anticoagulants and neuraxial injections. In Benzon HT, Raja S, Molloy RE, Liu SS, et al: Essentials of Pain Medicine and Regional Anesthesia. Elsevier–Churchill Livingstone, 2005, pp 708–720.
anticoagulation and peripheral nerve blocks

In contrast to neuraxial procedures in the presence of anticoagulants, there has been no studies on peripheral nerve blocks in the presence of anticoagulants. Nevertheless, there have been case reports of hematomas when peripheral blocks are performed in patients who were on these drugs.

One should realize that spontaneous hematomas in various locations have been reported in patients who took anticoagulants. These include hematomas of the abdominal wall, intracranial hemorrhage, and psoas hematoma with enoxaparin[80–82] andintrahepatic hemorrhage with LMWH.83 In fact, major hemorrhagic complications occur in 1.9% to 6.5% of patients on enoxaparin.84

A case of psoas hematoma and lumbar plexopathy was reported in a patient who was on enoxaparin and had a lumbar plexus block.85 The patient suffered a calcaneal fracture and was placed on enoxaparin 30 mg twice a day for deep vein thrombosis prophylaxis. In addition, she was on aspirin 325 mg a day. She had two surgeries for her calcaneal fracture, the first one was done under sciatic nerve block and the second under lumbar plexus block. She finally had a right below-the-knee amputation. Several attempts were made at lumbar plexus block, but the authors were unsuccessful, so a sciatic nerve block was ultimately performed. The enoxaparin was given 19.5 h before the block and 4.5 h after the block. The patient had hip pain and subsequently was unable to move her right leg. Computed tomography (CT) showed a right retroperitoneal hematoma involving the right psoas muscle. The enoxaparin was stopped and the hematoma was allowed to resorb. The patient regained motor function over the next 5 days and had no sensory or motor deficit at the 4-month follow-up visit.85 It should be noted that the timing of enoxaparin administrations were within the current ASRA guidelines.9 Although aspiration during the procedure
showed no blood, bleeding probably occurred during the attempts at lumbar plexus block. The intake of aspirin, in addition to the enoxaparin, probably contributed to the bleeding during the procedure. Other cases of retroperitoneal hematoma were reported after psoas compartment block.86 One was a patient who was given enoxaparin 30 mg the day after the block (postoperative day 2). The psoas catheter was removed 1 h, 40 min after the enoxaparin, at the peak effect of the drug. Another was a patient who was given heparin infusion 8 h after the block and warfarin (Coumadin) the evening of surgery (postoperative day 1). Both patients complained of paravertebral pain and CT scan showed a large psoas hematomas[86] Figure 7.

Figure 7. Right retroperitoneal hematoma displacing the kidney anteriorly. (Reprinted with permission from: Weller RS, Gerancher JC, Crews JC, Wade K. Extensive retroperitoneal hematoma without neurologic deficit in two patients who underwent lumbar plexus block and were later anticoagulated. Anesthesiology 2003; 98: 581–585.)

 

Clinical Pearls
  • The symptoms of hematoma formation after peripheral nerve block may include pain (flank or paravertebral pain or groin pain in psoas bleeding), tenderness in the area, steady decline in hemoglobin/hematocrit, hypotension due to hypovolemia), and sensory–motor deficit.
  • Definite diagnosis is made by CT.
  • Treatment may include surgical consultation, reversal of anticoagulation, blood transfusion as necessary, and watchful waiting versus surgical drainage.
  • It is probably too restrictive to adapt the same ASRA guidelines on neuraxial blocks to patients undergoing peripheral nerve blocks.

 

Bleeding after sympathetic block in patients on ticlopidine and clopidogrel have been reported.87 One patient had the block while on ticlopidine, the other patient had the block 3 days after clopidogrel was discontinued. Both patients complained of groin pain, one patient also had medial thigh numbness.87 Eventually, both patients were found to have retroperitoneal hematoma. Bleeding after intercostal block in a patient on heparin has also been reported.88

The symptoms of hematoma formation after peripheral nerve block may include pain (flank or paravertebral pain or groin pain in psoas bleeding), tenderness in the area, steady decline in hemoglobin/hematocrit, hypotension due to hypovolemia), and sensory–motor deficit. Definite diagnosis is made by CT; ultrasound can also be used to detect the presence of renal subcapsular hematomaafter psoas compartment block.89 Treatment may include surgical consultation, reversal of anticoagulation, blood transfusion as necessary, and watchful waiting versus surgical drainage.

It is probably too restrictive to adapt the same ASRA guidelines on neuraxial blocks to patients undergoing peripheral nerve blocks.9 The ASRA guidelines may be applicable to blocks in vascular and noncompressible areas such as celiac plexus blocks, superior hypogastric plexus blocks,and lumbar plexus blocks. Clinicians should individualize their decision and should discuss the risks and benefits of the block with the patient and the surgeon. Most important, the clinician should follow the patient closely after the block placement. Prospective studies are obviously needed to help guide clinicians in their decision.

References
  1. Tekkok IH, Cataltelpe O, Tahta K, et al: Extradural hematoma after continuous extradural anaesthesia. Br J Anaesth 1991;67:112–115.
  2. Hejazi N, Thaper PY, Hassler W: Nine cases of nontraumatic spinal epidural hematoma. Neurol Med Chir 1998;38:718–723.
  3. Dickman CA, Shedd SA, SpetzlerRF, et al: Spinal epidural hematoma associatedwith epidural anaesthesia:Complications of systemic heparinization in patients receiving peripheral vascular thrombolytic therapy. Anesthesiology 1990;72:947–950.
  4. Mattle H, Sieb JP, RohnerM, et al:Nontraumatic spinal epidural and subdural hematomas. Neurology 1987;37:1351–1356.
  5. Johnston RA: The management of acute spinal cord compression. J Neurol Neurosurg Psychiatry 1993;56:1046–1054.
  6. Wysowski DK, Talarico L, Balsanyi J, et al: Spinal and epidural hematoma and low-molecular-weight heparin. N Engl J Med 1998;338:1774–1775.
  7. Heit JA, Horlocker TT (eds): Neuraxial anesthesia and anticoagulation. Reg Anesth Pain Med 1998;23:S129–193.
  8. Horlocker TT,Wedel DJ: Anticoagulation and neuraxial block: Historical perspective, anesthetic implications, and risk management. Reg Anesth Pain Med 1998;23:129–134.
  9. Horlocker TT, Wedel DJ, Benzon HT: Regional anesthesia in the anticoagulated patient: Defining the risks (The second ASRA consensus conference on neuraxial anesthesia and anticoagulation). 2003;28:171–197.
  10. Benzon HT, Brunner EA, Vaisrub N: Bleeding time and nerve blocks after aspirin. Reg Anesth 1984;9:86–90.
  11. Rapaport SI: Preoperative hemostatic evaluation:Which tests, if any? Blood 1983;61: 229–231.
  12. Hindman BJ: Usefulness of the post-aspirin bleeding time. Anesthesiology 1986;64:368–370.
  13. Rodgers RPC, Levin J: A critical reappraisal of the bleeding time. Sem Thromb Hemost 1990;16:1–20.
  14. Ferraris VA, Swanson E: Aspirin usage and perioperative blood loss in patients undergoing unexpected operations. Surg Gyn Obst 1983;156:439–442.
  15. Cronberg S,Wallmark E, S¨oderberg I: Effect on platelet aggregation of oral administration of 10 non-steroidal analgesics to humans. Scand J Haematol 1984;33:155–159.
  16. Fressinaud E,Veyradier A, Truchaud F, et al: Screening for vonWillebrand disease with anew analyzer using high shear stress: A study of 60 cases. Blood 1998;91:1325–1331.
  17. Mammen EF, Comp PC, Gossselin R, et al: PFA-100 system. A new method for assessment of platelet dysfunction. SemThrombHemost 1998;24:195–202.
  18. Locke GE, Giorgio AJ, Biggers SL Jr, et al: Acute spinal epidural hematoma secondary to aspirin-induced prolonged bleeding. Surg Neurol 1976;5:293–296.
  19. Vandermeulen EP, Van Aken H, Vermylen J: Anticoagulants and spinal–epidural anesthesia. Anesth Analg 1994;79:1165–1177.
  20. CLASP (Collaborative Low-Dose Aspirin Study in Pregnancy) CollaborativeGroup. CLASP: A randomized trial of low-dose aspirin for the prevention and treatment of pre-eclampsiaamong9364 pregnant women. Lancet 1994;343:619–629.
  21. Horlocker TT,Wedel DJ, Offord KP: Does preoperatrive antiplatelet therapy increase the risk of hemorrhagic complications associated with regional anesthesia? Anesth Analg 1990;70:631–634.
  22. Horlocker TT, Wedel DJ, Schroeder DR, et al: Preoperative antiplatelet therapy does not increase the risk of spinal hematoma associated with regional anesthesia. Anesth Analg 1995;80:303– 309.
  23. Horlocker TT, Bajwa ZH, Ashraft Z, et al: Risk assessment of hemorrhagic complications associatedwith nonsteroidal antiinflammatory medications in ambulatory pain clinic patients undergoing epidural steroid injection. Anesth Analg 2002;95:1691–1697.
  24. Benzon HT, Wong HY, Siddiqui T, et al:. Caution in performing epidural injections in patients on several antiplatelet drugs. Anesthesiology 1999;91:1558–1559.
  25. EastwoodDW:Hematoma after epidural anesthesia: Relation of skin and spinal angiomas. Anesth Analg 1991;73:352–354.
  26. Greensite F, Katz J: Spinal subdural hematoma associated with attempted epidural anesthesia and subsequent spinal anesthesia. Anesth Analg 1980;59:72–73.
  27. Mayumi T, Dohi S: Spinal subarachnoid hematoma after lumbar puncture in a patient receiving antiplatelet therapy. Anesth Analg 1983;62:777–779.
  28. Gerancher JC, Waterer R, Middleton J: Transient paraparesis after postdural puncture spinal hematomain a patient receiving ketorolac. Anesthesiology 1997;86:490–494.
  29. UrmeyWF, Rowlingson JC: Do antiplatelet agents contribute to the development of perioperative spinal hematoma? Reg Anesth Pain Med 1998;23:146–151.
  30. Fitzgerald GA, Patrono C: The coxibs, selective inhibitors of cyclooxygenase-2. N Engl J Med 2001;345:433–442.
  31. McCrory CR, Lindahl SGE: Cyclooxygenase inhibition for postoperative analgesia. Anesth Analg 2002;95:169–176.
  32. Gajraj NM. Cyclooxygenase-2 inhibitors. Anesth Analg 2003;96:1720–1738.
  33. Buvanendran A, Kroin JS, Tuman KJ, et al: Effects of perioperative administration of a selective cyclooxygenase 2 inhibitor on pain management and recovery of function after knee replacement: A randomized controlled trial. JAMA 2003;290:2411–2418.
  34. Greenberg H, Gottesdiener K, Huntington M, et al: A new cyclooxygenase-2-inhibitor, rofecoxib (VIOXX) did not alter the antiplatelet effects of low-does aspirin in healthy volunteers. J Clin Pharmacol 2000;40:1509–1515.
  35. Lessee PT, Hubbard RC, Karim A, et al: Effects of celecoxib, a novel, cyclooxygenase-2-inhibitor, on platelet function in healthy adults: A randomized, clinical trial. J Clin Pharmacol 2000;40:124–132.
  36. van Heeken H, Schwartz JI, Depre M, et al: Comparative inhibitory activity of rofecoxib,meloxicam, diclofenac, ibuprofen and naproxen on COX-2 versus COX-1 in healthy volunteers. J Clin Pharmacol 2000;40:1109–1120.
  37. Reuben SS, Connelly NR: Postoperative analgesic effects of celecoxib or rofecoxib after spinal fusion surgery. Anesth Analg 2000;91:1221– 1225.
  38. Psaty BM, Furberg CD: Cox-2 inhibitors—Lessons in drug safety. New Engl J Med 2005;352:1133–1135.
  39. SchorK:Antiplatelet drugs:Acomparative review. Drugs 1995;50:7– 28.
  40. Lange RA, Hillis LD: Antiplatelet therapy for ischemic heart disease. N Engl J Med 2004;350:277–280.
  41. Boneu B, Destelle G, on behalf of the study group: Platelet antiaggregating activity and tolerance of clopidogrel in atherosclerotic patients. Thromb Haemost 1996;76:939–943.
  42. CAPRIE Steering Committee: A randomized blind trial of clopidogrel versus aspirin in patients at risk of ischaemic stroke (CAPRIE). Lancet 1996;348:1329–1339.
  43. Helft G, Osende JI,Worthley SG, et al: Acute antithrombotic effect of a front-loaded regimen of clopidogrel in patientswith atherosclerosis on aspirin. Arterioscler Thromb Vasc Biol 2000;29:2316–2321.
  44. Steinhubl SR, Berger PB,Mann JT, et al: Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: A randomized controlled trial. JAMA 2002;288:2411–2420.
  45. Mayumi T, Dohi S: Spinal subarachnoid hematoma after lumbar puncture in a patient receiving antiplatelet therapy. Anesth Analg 1983;62:777–779.
  46. BenzonHT,WongHY, SiddiquiT, et al: Caution inperformingepidural injections in patients on several antiplatelet drugs.Anesthesiology 1999;91:1558–1559.
  47. Shapiro SS: Treating thrombosis in the 21st century.New Engl JMed 2003;349:1762–1764.
  48. Enneking FK, Benzon HT: Oral anticoagulants and regional anesthesia: A perspective. Reg Anesth Pain Med 1998;23:140–145.
  49. Kearon C, Hirsh J: Management of anticoagulation before and after elective surgery. N Engl J Med 1997;336:1506–1511.
  50. Harrison L, Johnston M, Massicote MP, et al: Comparison of 5-mg and 10-mg doses in initiation of warfarin therapy. Ann Intern Med 1997;126:133–136.
  51. Benzon HT, Esposito P. Timing of removal of epidural catheters in anticoagulated patients. ASA annual meeting, San Diego, California, October 21, 1997. Anesthesiology 1997;87(3A):A798.
  52. Linn FH, Rinkel GJ, Algra A, et al: Incidence of subarachnoid hemorrhage: role of region, year, and rate of computed tomography: a meta-analysis. Stroke 1996;27:625–629.
  53. Odoom JA, Sih IL: Epidural analgesia and anticoagulant therapy. Anesthesia 1983;38:254–259.
  54. Horlocker TT,WedelDJ, Schlichting JL: Postoperative epidural analgesia and oral anticoagulant therapy. Anesth Analg 1994;79:89–93.
  55. Wu CL, Perkins FM: Oral anticoagulant prophylaxis and epidural catheter removal. Reg Anesth 1996;21:517–524.
  56. Horlocker TT: When to remove a spinal or epidural catheter in an anticoagulated patient. Reg Anesth 1993;18:264–265.
  57. Weinstock DM, Chang P, Aronson DL, et al: Comparison of plasma prothrombin and factor VII and urine prothrombin F1 concentrations in patients on long-term warfarin therapy and those in initial phase. Am J Hematol 1998;57:193–199.
  58. Jerkeman A, Astermark J, Hedner U, et al: Correlation between different intensities of anti-Vitamin K treatment and coagulation parameters. Thromb Res 2000;98:467–471.
  59. Rosenberg RD, Bauer KA: The heparin-antithrombin system: A natural anticoagulant mechanism. In Colma RW, Hirsch J, Marder VJ, et al (eds): Hemostasis and Thrombosis: Basic Principles and Clinical Practice, 3rd ed. JB Lippincott, 1994, pp 837–860.
  60. Abildgaard U, Lindahl AK, Sandset PM: Heparin requires both antithrombin and extrinsic pathway inhibitor for its anticoagulant effect in human blood. Haemostasis 1991;21:254–257.
  61. Murray DJ, Brodsnahan WJ, Pennell B, et al: Heparin detection by the activated coagulation time: A comparison of the sensitivity of coagulation tests and heparin assays. J Cardiothorac Vasc Anesth 1997;11:24–28.
  62. Shapiro SS. Treating thrombosis in the 21st century.New Engl JMed 2003;349:1762–1764.
  63. Weitz JI. Drug therapy: Low-molecular-weight heparins. N Engl J Med 1997;337:688–698.
  64. Rao TL, El-Etr AA: Anticoagulation following placement of epidural and subarachnoid catheters: An evaluation of neurologic sequelae. Anesthesisology 1981;55:618–620.
  65. Ruff DL, Dougherty JH: Complications of anticoagulation followed by anticoagulation. Stroke 1981;12:879–881.
  66. Liu SS, Mulroy MF: Neuraxial anesthesia and analgesia in the presence of standard heparin. Reg Anesth Pain Med 1998;23:157–163.
  67. Chaney MA: Intrathecal and epidural anesthesia and analgesia for cardiac surgery. Anesth Analg 1997;84:1211–1221.
  68. Weitz JI. Drug therapy: Low-molecular-weight heparins. N Engl J Med 1997;337:688–698.
  69. Horlocker TT,Heit JA: Lowmolecularweight heparin: Biochemistry, pharmacology, perioperative prophylaxis regimens, and guidelines for regional anesthetic management.AnesthAnalg 1997;85:874–885.
  70. Bara L, Billaud E, Gramond G, et al: Comparative pharmacokinetics of a low molecular weight heparin (PK 10 169) and unfractionated heparin after intravenous and subcutaneous administration.
    Thromb Res 1985;39:631–636.
  71. Klein S, Slaughter T, Vail PT, et al: Thrombelastography as a perioperative measure of anticoagulation resulting from low molecular weight heparin: A comparison with anti-Xa concentrations. Anesth Analg 2000;91:1091–1095.
  72. White RH. Low-molecular-weight heparins: are they all the same? Br J Haematology 2003;121:12–20.
    73.Horlocker TT,Wedel DJ: Neuraxial block and low molecular weight heparin: Balancing perioperative analgesia and thromboprophylaxis. Reg Anesth Pain Med 1998;23:164–177.
  73. Dickman CA, Shedd SA, SpetzlerRF, et al: Spinal epidural hematoma associated with epidural anesthesia: Complications of systemic heparinization in patients receiving peripheral vascular thrombolytic therapy. Anesthesiology 1990;72:947–950.
  74. Onishchuk JL, Carlsson C: Epidural hematoma associated with epidural anesthesia: Complications of anticoagulant therapy. Anesthesiology 1992;77:1221–1223.
  75. Rosenquist RW, Brown DL. Neuraxial bleeding: Fibrinolytics/ thrombolytics. Reg Anesth Pain Med 1998;23S:152–156.
  76. Bauer KA: Fondaparinux: Basic properties and efficacy and safety in venous thromboembolism prophylaxis. Am J Orthop 2002;31:4–10.
  77. TurpieAG,BauerKA, Eriksson BL, et al: Fondaparinux vs enoxaparin for the prevention of venous thromboembolism in major orthopedic surgery:Ameta-analysis of 4 randomized double-blind studies.Arch Intern Med 2002;162:1833–1840.
  78. TheMatisse Investigators: Subcutaneous fondaparinux versus intravenous unfractionated heparin in the initial treatment of pulmonary embolism. N Engl J Med 2003;349:1695–1702.
  79. Antonelli D, Fares L, Anene C: Enoxaparin associated with huge abdominal wall hematomas: A report of two cases. Am Surgeon 2000;66:797–800.
  80. Dickinson LD, Miller L, Patel CP, et al: Enoxaparin increases the incidence of postoperative intracranial hemorrhage when initiated preoperatively for deep vein thrombosis prophylaxis with brain tumors. Neurosurgery 1998;43:1074–1081.
  81. Ho KJ, Gawley SD, Young MR: Psoas hematoma and femoral neuropathy associated with enoxaparin therapy. Int J Clin Pract 2003;57:553–554.
  82. Houde JP, Steinberg G: Intrahepatic hemorrhage after use of lowmolecular-weight heparin for total hip arthroplasty. J Arthroplasty 1999;14:372–374.
  83. Noble S, Spencer CM: Enoxaparin: A review of its clinical potential in the management of coronary artery disease. Drugs; 1998;56:259– 272.
  84. Klein SM, D’Ercole F, Greengrass RA, et al: Enoxaparin associated with psoas hematoma and lumbar plexopathy after lumbar plexus block. Anesthesiology 1997;87:1576–1579.
  85. Weller RS, Gerancher JC, Crews JC, et al: Extensive retroperitoneal hematomawithoutneurologic deficit in two patientswho underwent lumbar plexus block and were later anticoagulated. Anesthesiology 2003;98:581–583.
  86. Maier C, Gleim M, Weiss T, et al: Severe bleeding following lumbar sympathetic blockade in two patients under medication with irreversible platelet aggregation inhibitors.Anesthesiology 2002;97:740– 743.
  87. Nielsen CH. Bleeding after intercostal nerve block in a patient anticoagulated with heparin. Anesthesiology 1989;71:162–164.
  88. Aida S, Takahashi H, Shimoji K: Renal subcapsular hematoma after lumbar plexus block. Anesthesiology 1996;84:452–455.

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DISCLAIMER: The material presented on this Web page has not been peer-reviewed. The indications, techniques and dosages on this Web page have been recommended in the medical literature and/or conform to OUR clinical practice. The medications and equipment have not necessarily been approved by the Food and Drug Administration (FDA) for use in the techniques and dosages for which they are recommended. The package insert for each drug and/or equipment should be consulted for use and dosage as recommended by the FDA. Because standards, practices and recommendations change, it is advisable to keep abreast of revised recommendations, particularly those concerning new drugs and techniques. While the techniques and dosages described are successfully used in our practice, they should be followed with a discretion since their complications may be dependent on the operator, patient and/or other accompanying clinical circumstances. The development and maintenance of this web page has not been supported by any pharmaceutical or medical manufacturing industry. The medications and/or equipment discussed in the web page is shown solely for teaching purposes. Similar equipment or medications from other manufacturers may produce similar clinical results to ours.