Blood Loss Management

Summary of Key Points

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Blood transfusion is no longer driven by the old 10/30 hemoglobin/hematocrit rule, and so little as even one unit of homologous blood transfusion has been found to increase the postoperative complication rate. Because of these new data, more stringent transfusion criteria are now in place.
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More than 50 drugs are approved that interfere with either the coagulation cascade or platelet function. Table 198-1 lists many of these drugs and gives useful data on managing these medications.
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Autotransfusion of autologous blood scavenged during surgery can lessen the need for homologous blood transfusion.
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Patient positioning using dedicated spine operating tables lessens blood loss by decompressing venous structures. This results in less epidural bleeding and less overall blood loss.
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The coagulation cascade can be manipulated with local or systemic agents to lessen blood loss during surgery.
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Potential operative blood loss should be calculated prior to surgery, blood products should be made available, and communication with the surgical team should include transfusion triggers and the clotting status of the patient.

Minimizing blood loss in spine surgery increases safety and improves patient outcomes. The causes for significant operative blood loss may be divided into two primary categories, which are not exclusive and typically work in concert. These are patient factors (e.g., habitus, epidural vascular anatomy, coagulation characteristics) and technical factors (e.g., number of levels, dissection technique, hemostatic control). Optimal mitigation of patient factors usually occurs prior to the date of surgery, through factors like weight loss, sufficient imaging, and evaluation and management of the coagulation profile. Conversely, the impact of technical factors is greatest in the immediate perioperative period. Blood loss and transfusion requirements are significantly affected by surgical technique, including duration of surgery, attention to hemostatic control, patient positioning, anesthetic techniques, and the pharmacologic agent used during surgery. Managing blood loss involves rational planning prior to and through the perioperative period, through attentive manipulation of these two primary categories of factors. A well-thought plan for managing blood loss will incorporate measures to optimize the clotting cascade, minimize intraoperative blood loss, and plan for the replacement of blood products through transfusion or intraoperative blood salvage. This chapter briefly reviews the physiology of hemostasis and then catalogs interventions available to the spine surgeon that can address these patient and technical factors so as to optimize hemostatic management.

Brief Review of Surgical Hemostasis

Surgical hemostasis is the controlled arrest of bleeding through physiologic (i.e., coagulation) and physical methods (i.e., ligation). The primary physiology at play in hemostasis is clot formation, which is a complex pathway of interconnected reactions. Reducing this complex system to its basic steps allows key components to be assessed with an aim toward improved hemostatic control. The first key step in this process is platelet activation, which occurs in response to exposed collagen in injured endothelium, thrombin, thromboxane A2, or adenine di-phosphate (ADP). The hemostatic plug, which forms in response to platelet activation in areas of endothelial injury, is termed primary hemostasis. Secondary hemostasis refers to the activation of the coagulation cascade, which ultimately produces a fibrin clot. As hemostasis progresses and a fibrin clot is formed, the fibrinolytic system is simultaneously activated to start the process of clot lysis ( tertiary hemostasis ) and thereby maintain a balance between clot formation and lysis. Critical to surgical hemostasis is the surgeon’s recognition of factors that will inhibit platelet function, thereby decreasing the effectiveness of primary hemostasis, as well as factors that inhibit the coagulation cascade, which in turn decreases secondary hemostasis. In addition, to physiologic methods, physical methods in terms of timely vessel ligation, (electro) coagulation or tamponade, and the reduction of hydrostatic pressure in the epidural system are also measures at the control of the surgical team, which can result in less surgical blood loss.

Preoperative Evaluation

A key component of the patient evaluation for spine surgery is a complete medical history. Special attention should be paid to medication history, as many medications interfere with primary and secondary hemostasis. Likewise, disease states such as renal failure, hematologic conditions, collagen disorders, and liver disease also affect hemostasis. These medical conditions should be diagnosed and optimized prior to surgery if possible. Patients with uncorrectable medical issues may be too ill for elective spine surgery, and clinical judgment will be required to balance the risks versus benefits. A chemistry panel will yield information on renal and hepatic function and may be useful for evaluation in specific patients. In patients with a personal or family history of bleeding disorder or those who report easing bruising, nose bleeds, menorrhagia, or multiple miscarriages or excessive blood loss with prior surgical procedures, a coagulation profile with coagulation times, platelet counts, and, in some instances, platelet function testing or a thromboelastogram should be obtained.

Preoperative anemia with hemoglobin levels less than 12 g/dl are associated with increased blood transfusion requirements and should be addressed if significant surgical blood loss is anticipated. Preoperative anemia may be treated with erythropoietin in combination with iron supplementation therapy and hematologist consultation. Consideration should be given to delaying elective surgical cases until the hemoglobin (Hgb) level exceeds 12 g/dL.

Tests of the coagulation system include platelet count, prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen, and the thromboelastogram (TEG). Platelet counts, platelet function, PT, and PTT should all be normal prior to surgery. Platelet function tests are used in special cases where abnormal platelet function is suspected, and they can be useful in timing surgery as they reveal when the antiplatelet effects of drugs have ended. The PTT and the PT measure multiple coagulation factors predicting coagulation deficits. The TEG has been used since the 1940s and became useful in guiding coagulation therapies in liver and aortic surgeries. TEG data are usually available within 30 minutes of draw time. Information on laboratory testing and terms is available in Box 198-1 .

Box 198-1

Laboratory Tests for Hemostasis in Surgery

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Prothrombin test (PT) measures coagulation factors VII, X, V, II, and I.
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Partial thromboplastin time (PTT) measures coagulation factors XII, XI, IX, VIII, X, V, II, and I.
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Platelet count measures the number of platelets in blood. Low levels suggest impaired function. Platelet count for spine surgery should be in the normal range listed on the specific lab where the test was completed. Typical counts for spine surgery should range from 150,000 to 400,000.
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Platelet function tests evaluate platelet function. Acquired platelet dysfunction from drugs can be monitored to assure normal platelet function prior to surgery.
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Complete blood count (CBC) measures hemoglobin, hematocrit, platelet count, as well as several other indices.
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Fibrinogen, factor I in the clotting cascade, is converted to fibrin by thrombin. Low fibrinogen levels are indicative of disseminated intravascular coagulation (DIC).
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D-Dimer indicates clot lysis and will be markedly elevated in cases of DIC.
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Thromboelastogram (TEG) evaluates the entire clot formation process from activation of platelets to clot formation, contraction, and fibrinolysis. It yields multiple data values. The r value, measured in minutes, reflects the reaction time delay from the initiation of the clotting process until the production of fibrin. The r value corresponds to the PT and PTT. Kinetic time (k) measures the time from initial fibrin formation to a specific amount of clot stiffness. This is the time in minutes from fibrin appearance at 2-mm thickness until a thickness of 20 mm has been achieved. The rate of fibrin formation is reflected in the alpha angle ( alpha ). This is measured by drawing a tangent from the zero axis on the graph measuring the r time and is a function of platelet count and fibrin levels as this angle reflects the interaction of activated platelets and fibrin as they form clot with a larger angle representing faster clot formation. Maximum amplitude refers to the maximum amount of clot formation and is a measurement of clot strength. Maximum angle mirrors platelet count and fibrin concentration so as in all types of materials thicker is stronger. Fibrinolysis is assessed with a value called lysis-30, which is the amount of clot that has dissolved within 30 minutes of reaching the maximum amplitude. Lysis-30 will reveal if fibrinolysis is occurring at an abnormally rapid rate. Recommendations for component replacement based on TEG values are as follows: for an r time of greater than 15 minutes infuse two units of fresh frozen plasma, for a maximum amplitude of less than 40 mm infuse 10 units of platelets, and for an alpha angle of less than 40 degrees infuse 6 units of cryoprecipitate. TEG can guide antifibrinolytic therapy, as Amicar or tranexamic acid will be of benefit in cases of hyperfibrinolysis. ( Gastroenterology & Hepatology Volume 8, Issue 8 August 2012)
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Metabolic panel measures serum chemistries and renal function with the blood urea nitrogen (BUN) and creatinine (Cr). Liver enzymes may also be contained, indicating abnormal liver function in some cases. Liver dysfunction and renal failure will affect clotting and hemostasis.

Medication History

Patients with a history of transient ischemic attack, stroke, deep venous thrombosis (DVT), heavy bleeding after minor trauma, alcoholism, hepatic dysfunction, neuromuscular scoliosis, cerebral palsy, and cardiac disease have an increased risk of bleeding either from the disease state or from pharmacologic therapies of their condition.

Patients who take warfarin (Coumadin) may require cessation or reversal of the anticoagulation in the acute setting. Oftentimes, under the guidance of their internist or hematologist, patients will be placed on a heparin (traditional or more commonly low-molecular-weight heparin) window to control the period of time in which anticoagulation for their underlying disease process is suspended to allow for safe spine surgical intervention while also minimizing the risk of a thrombotic event. Those rare patients with congenital coagulation deficits typically require consultation with a hematologist and often perioperative selective clotting factor replacement.

Multiple oral anticoagulant and antiplatelet drugs are emerging on the marketplace or are commonly in use. Knowledge of these medications is critical to preoperative planning. Many of these drugs have no known antidote or reversal agent. Platelet function can be impaired by drugs including aspirin (ASA), nonsteroidal anti-inflammatory drugs (NSAIDs), and specific platelet inhibitors. ASA can be held preoperatively in most patients without deleterious effects. However, patients with known coronary or cerebral vascular disease or significant risk factors for coronary artery disease should remain on ASA at a dose of 75 mg to 81 mg to lessen the risk of infarction in the perioperative period. Abrupt ASA cessation may cause a rebound effect on platelet aggregation, increasing risk of arterial thrombosis. In cases where ASA should be continued, surgical bleeding can be expected to be 1.5 times greater than normal, but the overall risk to the patient is lessened.

Nutritional supplements and herbs that inhibit platelet function include alfalfa, anise, bilberry, bladderwrack, bromelin, cat’s claw, celery, soleus, Cordyceps, dong quai, evening primrose oil, fenugreek, feverfew, garlic, ginger, ginkgo biloba, ginseng, grape seed, green tea, guggul, horse chestnut seed, horseradish, licorice, prickly ash, red clover, reishi, same, sweet clover, turmeric, and white willow. In general, all supplements should be held for 2 weeks prior to surgery, as their exact ingredients and their physiologic effects are highly variable and not well studied.

Table 198-1 contains a listing of medications that interfere with coagulation. The table lists antidotes where known and gives reported guidelines, estimating the amount of time that must pass before the anticoagulant effects of these medications abates. These estimates are based on the time to achieve three to four drug half-lives. The primary excretion path is annotated in the table to alert surgeons treating patients with renal failure/insufficiency or liver dysfunction to agents in which the time needed for coagulation to normalize will be increased. The estimated wait times after drug cessation reported in this table are longer than noted in other surgical literature, as spine surgeries are associated with greater blood loss than most other types of surgeries and this high estimated blood loss stresses the coagulation system more than small, less invasive procedures.

TABLE 198-1

Anticoagulants and Antiplatelets

Drug	Class	Mechanism of Action	Half Life	Antidote	Time to Stop Drug before Surgery	Excretion	Metabolism
Angiomax (Bibalirudin)	Anticoagulant	Reversibly inhibits thrombin	25 minutes	None	1 hour	Urine	Plasma
Argatroban	Anticoagulant	Direct thrombin inhibitor	51 minutes	None	2 hours	Feces 65%, Urine 22%	Liver
Arixtra (Fondaparinux)	Anticoagulant	Selective factor Xa inhibitor	21 hours	None	Recommended 24 hours before CABG, 4 days for spinal surgery	Urine	Unknown
Atryn (Antithrombin)	Anticoagulant	Inhibits thrombin and factor Xa neuralizes coagulant effects	17 hours	None	72 hours	Other	Unknown
Coumadin (Warfarin, Jantoven)	Anticoagulant	InhibitsVitamin K dependent factors II, VII, IX, X, Protein C, Protein S	Variable 20-60 hours	FFP, Vitamin K, Kcentra 25 u/Kg IV x 1	120 hours	Urine	Liver
Eliquis (Apixaban)	Anticoagulant	Factor Xa inhibitor	12 hours	Nospecific antidote, Charcoal if ingested within 2 hours, may try Prothrombin Complex concentrate and rVIIa, not dialyzable	36 hours	Urine 27%, Feces	Liver
Enoxaparin (Lovenox)	Anticoagulant	Binds to Antithrombin III inhibiting Factor X and Xa	7 hours	Protamine 1 mg IV for each mg of Enoxaparin given.	24 hours	Urine 40%	Liver
Fondaparinux	Anticoagulant	Binds to Antithrombin III inhibiting Factor X and Xa	21 hours	None	96 hours	Urine	Unknown
Fragmin (Dalteparin)	Anticoagulant	Binds to Antithrombin III inhibiting Factor X and Xa	5 hours	None	24 hours	Urine	Liver
Heparin	Anticoagulant	Binds to Antithrombin III Inactivates X	1.5 hours	Protamine 1 mg IV for each mg of heparin given.	6 hours	Urine	Liver
Inohep (Tinzaprin)	Anticoagulant	Unknown		None	Unknown	Urine	Unknown
Ipravisk (Desirudin)	Anticoagulant	Direct thrombin inhibitor	2 hours		6 hours	Urine	Kidney
Pradaxa (Dabigatran)	Anticoagulant	Directly reversibly inhibits thrombin	17 hours	Idarucizamab 5 g IV x1 (Praxbind)	72 hours	Urine	Liver
Refludan (Lepirudin)	Anticoagulant	Unknown/Drug not availaible in US		None	Unknown	Unknown	Unknown
Thrombate III (Antithrombin III)	Anticoagulant	Forms covalent bond with thrombin/only for use in congenital ATIII deficiency	3 days	None	Hematology Consult needed	Other	Unknown
Xarelto (Rivaroxaban)	Anticoagulant	Factor Xa inhibitor	9 hours	No specific antidote, not dialyzable, may try rVIIa, Prothrombin complex concentrate	36 hours	Urine 66% Feces 28%	Liver
Aggrastat (tirofiban)	Antiplatelet	Reversibly binds to platelet receptors IIb/Iia receptors reducing aggregation	2 hours		8 hours	Urine 65%, Feces 25%	minimal
Aggrenox (Aspirin/Dipyradamole)	Antiplatelet	See Aspirin and Dipyramole			See individual drugs
Agrylin (Anagrelide)	Antiplatelet	Disrupts megakaryocyte development reducing platelet count	1.3 hours		Used for Thrombocythemia, adjust dose to keep platelet counts below 600,000	Urine	Liver
Aspirin (Bayer Aspirin, Bayer low dose Aspirin, Bayer low dose Womens Aspirin, Bufferin, Ecotrin, Ecotrin low Strength, St Joseph, St Joseph regular Strength)	Antiplatelet, Salicylate	Nonselectively and irreversibly inhibits cyclooxygenase	6 hours		14 days	Urine	Liver
Brilinta (ticagrelor)	Antiplatelet	Reversibly binds reducing Platelet activation and aggregation	9 hours		7 days	Bile	Liver
Cilostazol (Pletal)	Antiplatelet	Reduces platelet aggregation, reversible	13 hours		5 days	Urine 74%, Feces 20%	Liver
Clopidogrel (Plavix)	Antiplatelet	Irreversibly binds to P2Y12 adenosine diphosphate receptors reducing platelet aggregation	8 hours		24 days	Urine 50%, Feces 46%	Liver
Dipyridamole (Persantine)	Antiplatelet	Inhibits platelet adenosine uptake reducing aggregation	10 hours		2 days	Bile	Liver
Effient (Prasugrel)	Antiplatelet	Irreversibly binds to P2Y12 adenosine diphosphate receptors reducing platelet aggregation	7 hours		28 hours	Urine 68%, Feces 27%	Liver
Integrilin (Eptifibatide)	Antiplatelet	Reversibly binds to platelet glycoprotein IIb/IIIa receptors reducing platelet aggregation	2.5 hours		5 hours	Urine 50%	minimal
Reopro (Abciximab)	Antiplatelet	Binds to platelet glycoprotein IIb/IIIa receotors reducing platelet aggregation	10 minutes		1 hour	Urine	Unknown
Ticlid (Ticlopidine)	Antiplatelet	Irreversibly binds to P2Y12 adenosine diphosphate receptors reducing platelet aggregation	5 days if repeated dosing	29 days	Urine 60%, Feces 23%	Liver
Ibuprofen (Advil, Motrin, Caldolor, Duexis)	NSAID	Reversibly Inhibits cyclooxygenase	2 hours		5 days	Urine	Liver
Naproxen (Aleve, Anaprox, Naprosyn, Vimovo, Treximet)	NSAID	Inhibits cyclooxygenase	17 hours		5 days	Urine	Liver
Flurbiprofen (Ansaid)	NSAID	Inhibits cyclooxygenase	8 hours		5 days	Urine 70%, Feces 30%
Diclofenac (Arthrotec, Cambia, Cataflam, Flector, Pennsaid, Voltaren, Zipsor, Zorvolex)	NSAID	Inhibits cyclooxygenase	2 hours		5 days	Urine 65%, Bile 35%	Liver
Celecoxib (Celebrex)	NSAID	Inhibits cyclooxygenase-2	11 hours		5 days	Feces 57%, Urine 27%	Liver
Sulindac (Clinoril)	NSAID	Inhibits cyclooxygenase	16 hours		5 days	Urine 50%, Feces 25%	Liver
Oxaprozin (Daypro)	NSAID	Inhibits cyclooxygenase	22 hours		5 days	Urine 65%, Feces 35%	Liver
Etodolac (Lodine)	NSAID	Reversibily inhibits cyclooxygenase 1 and 2	8 hours		5 days	Urine 73%
Meclofenamate	NSAID	Inhibits cyclooxygenase	1.3 hours		5 days	Urine 70%, Feces 30%	Liver
Mefenamic acid (Ponstel)	NSAID	Inhibits cyclooxygenase	2 hours		5 days	Urine 52%, Fexes 20%	Liver
Meloxicam (Mobic)	NSAID	Inhibits cyclooxygenase	20 hours		5 days	Urine, Feces	Liver
Nabumetone (Relafen)	NSAID	Reversibily inhibits cyclooxygenase 1 and 2	24 hours		5 days	Urine 80%
Ketorolac (Sprix, Toradol)	NSAID	Reversibily inhibits cyclooxygenase 1 and 2	2 to 19 hours		5 days	Urine 92%
Piroxicam (Feldene)	NSAID	Inhibits cyclooxygenase	50 hours		14 days	Urine, Feces	Liver
Fenoprofen (Naflon)	NSAID	Inhibits cyclooxegenase	3 hours		5 days	Urine 90%	Liver
Indomethicin (Indocin)	NSAID	Inhibits cyclooxegenase	12 hours		5 days	Urine 60%, Feces/bile 33%	Liver
Ketoprofen	NSAID	Inhibits cyclooxegenase	2 hours		5 days	Urine 90%	Liver
Tolmetin	NSAID	Inhibits cyclooxegenase	5 hours		5 days	Urine	Liver
Diflunisal (Dolobid)	Salicylate	Inhibits prostaglandin synthesis (reversible)	12 hours		2 days	Urine
Salsalate	Salicylate	Inhibits prostaglandin synthesis	16 hours		5 days	Urine	Liver
Valproic acid (Depakene)	Antiepileptic	Inhibits platelet function	16 hours		72 hours
Vorapaxar (Zontivity)	Antiplatelet	Inhibits PAR-1	13 days	No antidote	52 days	Feces