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Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_35_библиотеки_им_акад_М_И_Перельмана

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R. Jungerwirth et al.
cerebral autoregulatory dampening using NIRS and mean arterial blood pressure among infants who had DCC versus early cord clamping. They found that the DCC group had a signicantly more dynamic cerebral autoregulatory function and lower rate of IVH (OR 0.14, p<0.01) compared to the early cord clamping group. They postulate that DCC is neu­roprotective by stabilizing the cerebrovascular system and improving resistance to uctuations in systemic blood pres­sure [92].
Umbilical cord milking (stripping) may enable blood to more quickly be transferred from the placenta to the infant, reducing the time away from neonatal care during DCC.Among 40 preterm infants randomized to early cord clamping or clamping after umbilical cord milking, the milked group was less likely to be transfused and had a lower number of transfusions, higher initial hemoglobin, and higher mean blood pressure. The milked group also had a shorter duration of ventilation or supplemental oxygen, with no signicant difference in mortality [93].
A Cochrane review updated in 2019 of randomized con­trolled trials comparing early with delayed umbilical cord clamping for births before 37 weeks showed that delayed cord clamping may reduce the risk of death before discharge and any grade IVH for preterm infants, without sufcient evidence to show optimum timing of cord clamping or the effect of umbilical milking [94].
comes such as mortality, IVH, and NEC, with varying neuro­developmental outcomes. There was however an increased risk of ROP found in post-hoc analysis. Given the smaller reductions in transfusions and exposure with “likely...limited clinical importance,” the authors did not recommend EPO (darbepoetin required further study) in light of the possible increased risk of ROP [15].
Studies have found increased levels of EPO in vitreous uid when compared to serum. It has been proposed that EPO’s effect in preventing vascular apoptosis and stimulat­ing angiogenesis may be important in preventing ROP in its rst phase (when low IGF-1 levels prevent angiogenesis) and worsening proliferative ROP [97]. A retrospective cohort study of 327 low birth weight preterm infants found that recombinant EPO exposure was associated with an increased risk of progression of retinopathy (OR 1.27, 95% CI 1.04–1.55) [98]. Suk and colleagues also found that the infants who received more than 20 doses of recombinant EPO were at higher risk of developing ROP (OR 3.53, 95% CI 1.59–7.85); of note, infants treated with EPO starting after 20 days of age (compared to starting EPO before 20days) were similarly at higher risk (OR 3.57, 95% CI
1.59–8.03) [99].
Thrombocytopenia
Erythropoietin
Erythropoietin (EPO) and darbepoetin have been suggested as methods to reduce neonatal transfusion, given that prema­ture infants often have lower erythropoiesis and EPO levels. A randomized controlled trial of 157 preterm infants found that treating patients with recombinant human EPO versus placebo reduced the number (1.1 versus 1.6, p=0.046) and volume (16.5 versus 23.9mL, p=0.023) of blood transfu­sions. Despite this reduction in transfusion, patients given EPO had higher reticulocyte counts (p=0.0001) and hema­tocrit values (p=0.0001); they found no difference in the incidence of major complications of prematurity [95]. Ohls and colleagues further compared EPO to darbepoetin and placebo in a randomized trial of 80 low birth weight infants. They found that EPO and darbepoetin recipients had higher cognitive scores and lower incidence of cerebral palsy when compared to placebo [96].
A Cochrane review of EPO or darbepoetin effect on blood transfusions among preterm or low birth weight infants found that early EPO reduced the risk of transfusion (risk ratio 0.79, 95% CI 0.73–0.85), volume of transfusion (mean difference 7mL/kg, 95% CI 2–12), and number of donors to whom the infants were exposed (mean difference 0.54, 95% CI 0.20–0.89). There were no signicant differences in out-
Preterm infants are more likely to have thrombocytopenia compared to term infants [100]. Approximately 22–35% of neonates in NICU developed thrombocytopenia [101]. In addition to decreased platelet count, preterm neonates have platelet hyporeactivity for up to 3–4 days after birth. Thrombocytopenia is associated with bacterial and fungal infection, small for gestational age, low birth weight, preg­nancy-induced hypertension, necrotizing enterocolitis, and DIC [102]. Thrombocytopenic babies also have signicantly more skin, renal, pulmonary, or CNS hemorrhage, as well as higher mortality rate [100].
Causes/Risk Factors
Neonatal thrombocytopenia is dened as less than 150,000/ mL [104]. Marked thrombocytopenia is dened as less than 100,000/mL, and severe thrombocytopenia is less than 50,000/mL.However, a study in 2009 suggested that the cut­off for neonatal thrombocytopenia may need to be revised, as normal platelet counts can fall below 150,000 and still be within the reference range of 5th–95th percentiles [100].
Thrombocytopenia can be divided into early onset (within 3 days of birth) and late onset (>3 days after birth) [5]. Causes of early onset thrombocytopenia are prenatal factors such as severe intrauterine growth restriction and maternal
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factors such as preeclampsia, HELLP syndrome, immune thrombocytopenia, pregnancy-induced hypertension, sys­tematic lupus erythematosus, and cancer [103]. Late-onset thrombocytopenia can be caused by bacterial sepsis, necro­tizing enterocolitis, or thrombotic events associated with the use of central lines [104].
The mechanisms of thrombocytopenia include decreased production, increased platelet consumption, increased extra­vascular loss, or a combination of these factors. Preterm infants with thrombocytopenia had fewer circulating mega­karyocyte progenitors, compared to non-thrombocytopenic counterparts. Small for gestational age (SGA) neonates are also at risk for developing thrombocytopenia in the rst week after birth [105]. A third of SGA infants have early thrombocytopenia. About 10% of these neonates have an obvious cause of thrombocytopenia, whereas 90% have thrombocytopenia that is hyporegenerative rather than plate­let consumption or destruction [105]. Transplacental passage of maternal allo antibodies and auto-antibodies is responsi­ble for 9–20% of all neonatal thrombocytopenias [106].
Very low birth rate infants have the highest rate of IVH, up to 25% [107]. Severe thrombocytopenia predisposes infants to intraventricular brain hemorrhage, but most preterm infants who develop a severe IVH do not have thrombocytopenia before their IVH, but rather develop thrombocytopenia and coagulopathy after the IVH [102]. IVH cause thrombocytopenia by increased consumption. Thrombocytopenia (platelet count below 150×109/L) is a risk factor for IVH among VLBW infants (hazard ratio of
2.17), but there was no relationship between severity of thrombocytopenia and risk of subsequent IVH.
Treatment (Platelet Transfusion)
Consider the condition of the neonate and the platelet count. Stable neonates have a much lower risk of ICH [102]. Among the different studies, there is no consensus in regard to the exact threshold to transfuse.
factor. Majority (84%) of platelet transfusions were given to neonates with either no bleeding or only minor bleeding [
There was a randomized controlled trial that compared higher (<150×10^9/L) and lower (<50×10^9/L) platelet count thresholds for prophylactic transfusion. The incidence of ICH did not differ between the two groups. Early prophy­lactic platelet transfusion did not reduce the incidence or extent of intracranial hemorrhage [108].
A recent large randomized prospective multicenter trial of platelet transfusion thresholds in preterm infants showed that those transfused at a threshold of 50,000 cubic millimeter vs 25,000 cubic millimeter had a higher incidence of death or major bleeding up to day 28 of life. The odds ratio is 1.57 (95% condence interval, 1.06–2.32; P=0.02). Reasons for this difference is unknown. It could be 2/2 immunologic and inammatory effects of platelets. This suggests that a restric­tive platelet transfusion trigger may be preferable [109].
Platelet transfusion should not be given to patients with low risk of IVH for the sole purpose of maintaining platelet count above an arbitrary level. The mortality rate of infants who received transfusion is twice that of those who did not receive transfusions, although the mortality rate is likely sec­ondary to underlying illness rather than negative effects of transfusion [ number of platelet transfusions [103]. Severity of thrombo­cytopenia did not correlate with risk for IVH [110].
3]. Furthermore, mortality is associated with
5].
Transfusion Markers
Immature platelet fraction is a marker for megakaryopoietic activity in neonates and reects the platelet production rate. The IPF can be useful in predicting the course of thrombocy­topenia and can identify patients at risk of severe drop in platelet count. This information is helpful for identifying which neonates would benet from platelet transfusions [111].
Complications
Thresholds
An observational study showed that of the neonates that had severe neonatal thrombocytopenia (platelet count <60×10^9 platelets/L), approximately 1/3 of them had platelet counts as low as <20×10^9. However, only 9% of these neonates developed major hemorrhage. There was no signicant cor­relation between nadir of platelet count and risk of major hemorrhage. The majority of neonates that had major hemor­rhage were gestational ages <28weeks (85% of those with hemorrhage) and were within 14days of birth. This suggests that gestational age and postnatal age were more of a risk
Platelet transfusion can worsen outcome in NEC [112]. Other risks of transfusion include bacterial contamination and CMV infection. Ways to decrease risk of platelet trans­fusion include photochemical inactivation by crosslinking DNA and RNA of viruses, bacteria, and host cells [107].
Treatment Alternatives
Alternative to transfusion includes recombinant human thrombopoietin (TPO). Thrombopoietin (Tpo) is the pri­mary regulator of megakaryopoiesis and platelet produc-
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tion [100]. However, some patients developed anti-Tpo antibodies which can lead to aplastic anemia and severe hyporegenerative thrombocytopenia [113]. There are two thrombopoietin receptor agonists, eltrombopag and romip­lostim, that have been approved by the FDA, but only few neonates have been treated with these agents [3]. Furthermore, Tpo receptor agonists require 7–10 days between commencement of dosing and a signicant increase in platelet count [105].
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88. Mercer JS, Vohr BR, McGrath MM, etal. Delayed cord clamping in very preterm infants reduces the incidence of intraventricular hemorrhage and late-onset sepsis: a randomized, controlled trial. Pediatrics. 2006;117(4):1235–42.
89. Song D, Jegatheesan P, DeSandre G, Govindaswami B.Duration of cord clamping and neonatal outcomes in very preterm infants. PLoS One. 2015;10(9):1–10.
90. Strauss RG, Mock DM, Johnson KJ, etal. A randomized clinical trial comparing immediate versus delayed clamping of the umbili­cal cord in preterm infants: short-term clinical and laboratory end­points. Transfusion. 2008;48:658–65.
91. Lodha A, Shah PS, Soraisham AS, etal. Association of deferred vs immediate cord clamping with severe neurological injury and survival in extremely low-gestation-age neonates. JAMA Netw Open. 2019;2(3):e191286.
92. Vesoulis ZA, Liao SM, Mathur AM. Delayed cord clamping is associated with improved dynamic cerebral autoregulation and decreased incidence of intraventricular hemorrhage in preterm infants. J Appl Physiol. 2019;127:103–10.
93. Hosono S, Mugishima H, Fujita H, etal. Umbilical cord milking reduces the need for red cell transfusions and improves neona­tal adaptation in infants born at less than 29 weeks’ gestation: a randomized controlled trial. Arch Dis Child Fetal Neonatal Ed. 2008;93:F14–9.
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96. Ohls RK, Kamath-Rayne BD, Christensen RD, et al. Cognitive outcomes of preterm infants randomized to darbepoetin, erythro­poietin, or placebo. Pediatrics. 2014;133(6):1023–30.
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Overview oftheCoagulation Cascade
Coagulation is the intricate process of clot formation that is fundamental in preventing bleeding and facilitating healing. This process is initiated by primary hemostasis, which entails platelet adhesion, aggregation, and plug formation. A plate­let plug has the dual capability of activating the coagulation cascade while also being an unstable, temporary measure for bleeding cessation [3, 4]. The relationship between platelets and the coagulation cascade illustrates the importance of acknowledging the inuence some antiplatelets may have on regional anesthesia.
Anticoagulants operate by inhibiting certain aspects of the coagulation cascade. The coagulation cascade is com­posed of calcium, phospholipids, and coagulation proteins. The proteins, also known as clotting factors, are sequentially activated into serine proteases to ultimately develop a brin clot. Clot formation is achieved through two collaborating pathways: extrinsic and intrinsic. Initiated by endothelial damage and exposure of blood to an articial surface, the intrinsic pathway begins with the transformation of factor XII into its activated serine protease, factor XIIa [5]. Factor XIIa then serves as a stimulant of the downstream generation of activated factors XI and IX.Factor IXa forms a complex with factor VIII, as its cofactor, to activate factor X to factor Xa (Fig 44.1) [4, 5].
The extrinsic pathway is also initiated by vascular insult but through the release of tissue factor from endothelial cells. Tissue factor then activates factor VII to factor VIIa, and together they activate factor X to factor Xa, which is the
C. Cherenfant Weill Cornell Medicine, Department of Anesthesiology, New York, NY, USA
U. Umeh ( NYU Langone Health, NYU Langone Orthopedic Hospital, Department of Anesthesiology, Perioperative Care and Pain Medicine, New York, NY, USA e-mail: Uchenna.umeh@nyulangone.org
*)
converging point of both pathways [6, 7]. This convergence continues as the “common pathway” [3, 4, 8]. Thereafter, factor Xa is aided by factor Va as a cofactor to activate and cleave prothrombin (factor II) into thrombin (factor IIa). Thrombin then cleaves brinogen to brin (factor Ia). Thereafter, brin monomers aggregate with each other to form a brin mesh that stabilizes the platelet plug to facili­tate the goal of the coagulation cascade and ultimately gen­erate a brin clot [5–8].
Anticoagulants andIts Implications onRegional Anesthesia
Regional anesthesia encompasses spinal anesthesia, epidural anesthesia, and nerve blocks [9, 10]. Examples of surgeries that benet from regional anesthesia include hip, knee, ankle, breast, thoracic, major abdominal, and cesarean sections [11–13]. As with most medical interventions, it is always important to weigh the benets versus the risks of regional anesthesia. A major, yet rare, complication that may occur is a hematoma in the spinal or epidural space and its associated neurological complications [9, 14–16]. Thus, it is crucial to be cognizant of the risk factors that may make this occur­rence more likely. Certainly, a patient’s use of anticoagulants augments the possibility of bleeding and, similarly, spinal hematomas. To address this concern, guidelines have been developed to aid anesthesiologists in providing their patients with the benets of regional anesthesia while diminishing the risks. The majority of guidelines mentioned in this chap­ter will be from the latest American Society of Regional Anesthesia and Pain Medicine (ASRA) guidelines from
2018. Fundamentally, these guidelines are evidence-based recommendations that assist anesthesiologists and other healthcare providers in executing safe peripheral and neur­axial regional anesthetic care [9, 17–20].
© Springer Nature Switzerland AG 2021 C. S. Scher et al. (eds.), Essentials of Blood Product Management in Anesthesia Practice,
https://doi.org/10.1007/978-3-030-59295-0_44
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Fig. 44.1 Coagulation
cascade
C. Cherenfant and U. Umeh
Heparin: Unfractionated andLow Molecular Weight
Heparin and its derivatives interfere with the coagulation cascade by binding to antithrombin, which inactivates throm­bin (factor IIa), factor Xa, and factor IXa. Consequently, the brin clot is not formed [21, 22]. Heparin’s anticoagulant effects can be reversed by protamine, with LMWH requiring more time for reversal due to reduced protamine binding. When given therapeutically, heparin can be monitored by partial thromboplastin time (PTT) and more accurately by anti-factor Xa. However, for neuraxial blocks, anti-factor Xa has not been found to be a predictor of the risk of bleeding. Since a specic level of anti-factor Xa has yet to be deter­mined for optimal regional anesthesia, it is therefore not rec­ommended as a mode of monitoring LMWH. During
cardiopulmonary bypass, activated clotting time (ACT) is used to monitor the higher doses of heparin use.
Unfractionated heparin (UFH) and low molecular weight heparin (LMWH) have different biochemical and pharmaco­logical properties, with LMWH often being preferred over UFH.LMWH has more favorable properties such as longer half-life, lower risk of hemorrhagic side effects, and more predictable pharmacokinetics [23, 24].
ASRA recommendations for spinal anesthesia with unfractionated heparin use include the following [9]:
• Discontinuing intravenous heparin 4–6 hours prior to
neuraxial blockade.
• Verifying normal coagulation.
• Delaying heparin administration for at least 1hour after
needle placement.
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• Removing neuraxial catheters 4–6 hours after the last heparin dose.
• Monitor the patient postoperatively to provide early detection of motor blockade, and consider the use of min­imal concentration of local anesthetics to enhance the early detection of spinal hematoma.
• In the setting of more than a 4-day course of either UFH or LMWH, it is recommended to obtain a platelet count prior to neuraxial block or catheter removal, in light of the possibility of heparin-induced thrombocytopenia.
Of note, subcutaneous (SC) unfractionated heparin has
different recommendations based on its dosing. For low-dose UFH with doses of 5000units BID or TID, neuraxial block should occur 4–6hours after last dose. There is no contrain­dication in maintaining catheters in the setting of low-dose UFH postoperatively. For higher doses such as 7500– 1000units BID or a daily dose greater than 20,000units, it is suggested that neuraxial anesthesia occur 12 hours later. Postoperatively, these higher doses of UFH and their safety with indwelling neuraxial catheters have not been estab­lished. Thus, the management of these patients must be based on individual assessment of the risks and benets [9].
The recommendations for spinal anesthesia among
patients who use low molecular weight heparin are different from those regarding UFH. The difference in guidelines exist because of their distinct pharmacological proles and knowledge acquired from case reports and clinical data. This data allowed the FDA to create a Drug and Safety Communication in 2013 that entailed updated information on LMWH, with the goal of decreasing the risk of neuraxial hematoma and paralysis. Interestingly, for LMWH, anes­thetic and patient risk factors associated with spinal hemato­mas were ascertained such as female sex, age greater than 65, epidural technique, early postoperative administration (<12hours), and greater than one dose daily [25]. Notable ASRA recommendations regarding low molecular weight heparin include the following [9]:
• Needle placement should occur at least 12hours after a prophylactic LMWH dose.
• LMWH prophylactic dose should be administered no ear­lier than 12hours after catheter/needle placement. If there is a second dose to be given, it should be administered at least 24 hours after the rst dose. Remove the catheter 12hours after the last dose of LMWH.
• If a dose of LMWH was given preoperatively within 2hours, refraining from neuraxial technique is ideal, as needle placement would occur near peak anticoagulant activity.
• A delay of at least 24hours prior to needle/catheter place­ment is recommended for higher (therapeutic) doses of LMWH (enoxaparin 1mg/kg every 12hours, enoxaparin
1.5 mg/kg daily, dalteparin 120 U/kg every 12 hours, dalteparin 200U/kg daily, or tinzaparin 175U/kg daily).
• After surgery with non-high bleeding risk, therapeutic dose of LMWH can be resumed in 24 hours. For high bleeding risk surgery, therapeutic dose LMWH can be reinstituted 48–72hours after.
Warfarin
Warfarin is an oral anticoagulant that affects the clotting cas­cade by interfering with the synthesis of clotting factors II, VII, IX, and X.This is done by warfarin’s ability to inhibit vitamin K epoxide reductase, which is necessary in the development of specic clotting factors from the liver [26]. Thus, warfarin’s inhibition of vitamin K leads to decreased clotting factors and clot development by impeding both the intrinsic and extrinsic pathways. The anticoagulant effect of warfarin can be monitored by prothrombin time (PT) and international normalized ratio (INR). Warfarin can be reversed by fresh frozen plasma (FFP), prothrombin complex concentrate (PCC), and vitamin K [27]. PCC can be catego­rized as three-factor with factors II, IX, and X or four-factor consisting of factors II, VII, IX, and X.PCC may also be composed of protein C and S and heparin whose purpose is to balance the large clotting factor concentration that can be 25 times higher than that in normal plasma [28].
ASRA recommendations for regional anesthetic manage-
ment for patients on warfarin are as follows [9]:
• Stop warfarin ideally up to 5 days prior to a neuraxial block and with INR normalization.
• Perform routine testing of sensory and motor function during epidural analgesia for patients on warfarin therapy, with the use of anesthesia that minimizes sensory and motor blockade.
• In the setting of reinitiating warfarin thromboprophylaxis, remove neuraxial catheters when INR is less than 1.5. Of note, although this recommendation was based on labora­tory and clinical data, the risk of an INR greater than 1.5 but less than 3 is unknown.
• Hold or reduce warfarin in patients with indwelling cath­eters with an INR greater than 3.
• Continue neurologic assessment at least 24 hours after catheter removal.
Fondaparinux
Fondaparinux is an injectable synthetic pentasaccharide. Its benets include rapid absorption, lack of platelet interaction, and a long half-life of 17–21hours that allows for one-time
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dosing. However, a detriment of its use is that there is no reversal or antidote [29]. Fondaparinux’s anticoagulant effect is that it inhibits factor Xa. During the initial clinical trials that helped determine the dose ranging of fondaparinux, no spinal hematomas were reported. This occurred because strict parameters were used such as patients being excluded from the study if needle placement was not accomplished on the rst attempt or if there was traumatic bleeding. Therefore, the true risk of fondaparinux use on regional anesthesia is unknown, which provides more insight to the ASRA recom­mendations [9]:
• Until further clinical experience is available, performance of neuraxial technique should occur under the conditions used in clinical trials (single needle pass, avoidance of indwelling neuraxial catheters, atraumatic needle place­ment). If this is not feasible, an alternate method of pro­phylaxis should be considered.
• Neuraxial catheters should be removed 6hours prior to the rst postoperative dose.
Direct Parental Thrombin Inhibitors
Desirudin, bivalirudin, and argatroban are parenteral antico­agulants commonly used for treating heparin-induced throm­bocytopenia. They all share the anticoagulant mechanism of inhibiting thrombin. Their effect can be monitored by acti­vated PTT, and there is no pharmacological reversal. Due to the lack of information available to determine patient man­agement and risk, ASRA recommends against the perfor­mance of neuraxial anesthesia in patients receiving these parenteral thrombin inhibitors [9].
Novel Oral Anticoagulants
Novel oral anticoagulants or non-vitamin K antagonist oral anticoagulants, also known as NOACs, are increasingly used due to many advantages. NOACs can be given without the need for monitoring. They are associated with less intracra­nial bleeding and more rapid onset and are often just as effective in preventing clots such as those seen in venous thromboembolism. NOACs include dabigatran, apixaban, betrixaban, edoxaban, and rivaroxaban [30–33].
Dabigatran is an oral direct thrombin inhibitor with a
half-life of 12–17hours. More than 80% of it is renally elim­inated. The most reliable monitoring of dabigatran is by thrombin time (TT), ecarin clotting time (ECT), and diluted thrombin time (dTT) [34]. In 2015, the FDA approved idaru­cizumab as a rapid reversal of dabigatran. Idarucizumab is a monoclonal antibody that is a non-competitive irreversible inhibitor of the dabigatran-thrombin complex that works in
minutes [ advised against placing epidural catheters due to limited experience, which consequently led to limited data on dabi­gatran and neuraxial anesthesia. However, with increased understanding of its pharmacokinetics and expert opinion, recommendations on neuraxial anesthesia amidst dabigatran use have been made. Of note, the suggestions are largely inuenced by the renal excretion of dabigatran. The ASRA guidelines state [9]:
• We suggest that dabigatran be discontinued 120 hours
• We suggest removing neuraxial catheters 6hours before
• Before removing an indwelling catheter during adminis-
NOACs that exhibit their anticoagulant effects by inhibiting factor Xa. Therefore, the best mechanism of monitoring their effect is by anti-factor Xa assays [9]. There are recently developed reversals for NOACs: idarucizumab, andexanet, and ciraparantag. Idarucizumab was previously discussed as a reversal agent for dabigatran. Andexanet binds to apixa­ban, edoxaban, rivaroxaban, and betrixaban as a decoy receptor, thereby inhibiting their mechanisms of action. It also reverses the antithrombotic effects of low molecular weight heparin, unfractionated heparin, and fondaparinux. Lastly, ciraparantag/aripazine uses its hydrogen bonding sites to bind to and reverse all NOACs and heparin [35, 36]. Since these reversals are fairly new and ciraparantag is still under investigation. Other antidotes are often used such as recombinant coagulation factor VIIa and PCC, which is a known reversal for warfarin [37]. Factor eight inhibitor bypassing activity (FEIBA) is another reversal agent that stops bleeding by generating thrombus due to its composi­tion of factors II, IX, X, and VIIa, prothrombin, and pro­thrombin complex factors [38].
35]. Initially, the manufacturer of dabigatran
prior to neuraxial block. However, if renal function has been reliably determined, and there are no additional risk factors for bleeding (e.g., age>65 years, hypertension, concomitant antiplatelet medications), a more graded approach may be considered:
– For all suggestions, consider checking ecarin clotting
time and diluted thrombin time. However, an accept­able level of residual dabigatran activity to proceed with neuraxial block remains undetermined.
– In patients with creatinine clearance (CrCl) 80mL/min
or greater, discontinue dabigatran 72hours prior neur-
axial block. – In CrCl of 50–79mL/min, discontinue 96hours prior. – In CrCl of 30–49mL/min, discontinue 120hours prior. – We suggest against the performance of neuraxial
blocks in patients with a CrCl less than 30mL/min.
rst postoperative dose.
tration, hold dabigatran for 34–36hours or assess dTT or ECT.
Rivaroxaban, apixaban, edoxaban, and betrixaban are all
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ASRA suggested management for patients on rivaroxa-
ban as follows [9]:
• Discontinue rivaroxaban 72 hours prior to neuraxial block. Consider checking rivaroxaban or anti-factor Xa activity level if less than 72hours. An acceptable level of residual rivaroxaban activity to proceed with neuraxial block remains undetermined.
• Remove neuraxial catheters 6hours prior to the rst post­operative dose.
• With unanticipated administration with indwelling cathe­ter, hold rivaroxaban dosing 22–26hours before catheter removal, or assess an anti-factor Xa assay calibrated to rivaroxaban until the catheter is removed.
ASRA suggested management for patients on apixaban as
follows [9]:
• Discontinue apixaban 72hours prior to neuraxial block. Consider checking apixaban or anti-factor Xa activity level if less than 72hours. An acceptable level of residual apixaban activity to proceed with neuraxial block remains undetermined.
• Remove catheters 6hours prior to the rst postoperative dose.
• With unanticipated administration with indwelling cath­eter, hold apixaban dosing for 26–30hours, or calibrate an anti-factor Xa assay to apixaban before catheter removal.
ASRA suggested management for patients on edoxaban
as follows [9]:
• Discontinue 72 hours prior to neuraxial block. Consider checking edoxaban or anti-factor Xa activity level if less than 72hours. An acceptable level of residual edoxaban activity to proceed with neuraxial block remains undetermined.
• Remove neuraxial catheters 6hours prior to the rst post­operative dose.
• Hold edoxaban for 20–28hours, or perform an anti-factor Xa assay calibrated to edoxaban before catheter removal.
Thrombolytic Therapy
Thrombolytics, also known as brinolytics, dissolve brin clots through the action of plasmin. Plasmin is derived from its inactive precursor plasminogen. Plasmin’s mechanism of action is dissolving brin clots. This results in brin degradation products that inhibit platelet aggregation, furthering their role in anticoagulation. Examples of thrombolytics include exogenous plasminogen activators such as streptokinase and urokinase and formulations of tissue plasminogen activator (t-PA) like alteplase and tenecteplase. Plasminogen activators incite the reaction of plasminogen to plasmin and dissolve brin, thereby decreas­ing the amount of both brin and plasminogen. t-PA is more brin selective, where it binds to brin stimulating the dis­solving of clots [9, 39, 40].
In patients taking brinolytics, ASRA recommends the
following [9]:
• Against spinal or epidural anesthesia except in “highly unusual circumstances” [9].
• A 48-hour time interval and documentation of normaliza­tion of clotting studies, like brinogen, is suggested between discontinuation of these medications and the time of neuraxial puncture. This is because brinogen can be used to determine residual thrombolytic effect since it is one of the latter clotting factors to recover. It is also noted that puncture of “noncompressible vessels” was an original contraindication to thrombolytic therapy, with a now suggestion of 10days following puncture for therapy.
• In patients who receive neuraxial anesthesia during or near the time of thrombolytic use, it is recommended for them to undergo neurological checks, no more than 2 hours apart. In this setting, if the anesthesia is an epidural catheter infusion, the anesthetic should have minimal sensory and motor block to allow for neurological monitoring.
• There is no recommendation for removal of neuraxial catheters in patients who receive thrombolytics unexpectedly, yet it is suggested to measure brinogen level.
ASRA suggested management for patients on betrixaban
as follows [9]:
• Discontinue a minimum of 72hours prior to a neuraxial block. Consider checking betrixaban or anti-factor Xa level if less than 72hours.
• There is a suggestion against the performance of neurax­ial blocks in patients with CrCl less than 30mL/min.
• Remove neuraxial catheters 5hours prior to next dose.
• With indwelling catheter, hold betrixaban dose for 72hours, and then remove the catheter.
Antiplatelets
Antiplatelet medications include nonsteroidal anti­inammatory drugs (NSAIDs), aspirin, platelet receptor antagonists, and platelet phosphodiesterase IIIA inhibitors. NSAIDs and aspirin have not been found to increase risks for complications related to regional anesthesia, due to their minimal effect on platelet function. Therefore, there are no recommendations for timing of anesthesia administration or catheter techniques for patients on aspirin or NSAIDs [9,
41]. However, ASRA cautions performing regional anesthesia
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