New Thoughts on Bleeding and Coagulation Disorders

Moeen K. Panni

Introduction

Pregnancy induces a protective hypercoagulable state (1) in preparation for the potential bleeding that may occur during delivery of the fetus (2). There are a number of clinical disorders occurring in pregnancy, however, that can predispose to bleeding, many of which are related to thrombocytopenic syndromes (3). Neuraxial anesthesia has been shown to be the optimal anesthetic technique for most parturients; however, it carries with it the risk of subsequent epidural hematoma formation, particularly in those with abnormalities in processes that prevent bleeding.

As newer and more potent anticoagulant medications have been introduced, many of which are used in parturients, additional risk of bleeding in the epidural space after neuraxial anesthesia now exists. While bleeding time studies are no longer routinely used clinically, due to their inaccuracy in predicting bleeding risks, the common standard laboratory coagulation tests such as prothrombin time (PT) and partial thromboplastin time (PTT) that are used, are limited in their application in the assessment of the risks of bleeding, especially in patients receiving these newer anticoagulant and antiplatelet medications. Point-of-care tests such as the thromboelastogram TEG® and TEG® Platelet Mapping™ assay (Haemoscope Corporation, Niles, IL, US), Sonoclot® Coagulation & Platelet Function Analyzer (Sienco Inc., Arvada, CO), Hemodyne™ Hemostasis Analyzer (Hemodyne, Richmond, VA), and platelet functional analyzers such as PFA-100® (Dade-Behring, Dudingen, Switzerland) (4), the first three of which assay the entire coagulation system, are important tools in the anesthesiologist’s repertoire to evaluate the risks of bleeding and benefits of using neuraxial techniques.

Anesthesia Options for the Obstetric Patient

There are a number of choices available to achieve analgesia during labor as well as anesthesia during operative delivery in obstetrics (5). Neuraxial techniques are safe and extremely effective in relieving labor pain; and they are the preferred methods of anesthesia in the obstetric operating room. While these are safe, as with all anesthetic techniques, there are definite risks associated with them that need to be balanced by the benefits of performing such procedures.

The choice of anesthetic technique selected in the obstetric operating room is based upon the clinical scenario that is presented and is influenced by several factors, including but not limited to the timing of cesarean delivery (elective, urgent, or emergent) as well as the indications for cesarean delivery (maternal, fetal, or both). If possible, instrumentation of the pregnant airway is avoided and neuraxial anesthesia is used whenever it is clinically feasible, weighing the risks and benefits for each patient and clinical scenario. General anesthesia in the obstetric patient carries with it a markedly increased incidence of difficult airway compared to the non-obstetric patient (1:∼300 vs.1:∼2,000) (6), increased aspiration risk (7), chance of higher awareness under general anesthesia than in a non-obstetric patient (8), potentially detrimental anesthetic effects on the fetus, (9) and lack of maternal participation in the birth process (10). All of these reasons suggest that a regional technique should be chosen whenever possible.

The effects of anesthetic agents on obstetric patients have been debated since 1847 when James Simpson first described his use of inhalational labor analgesia in Scotland (11), shortly after the first public demonstration of ether anesthesia in Boston. While the increasing use of regional anesthesia has led to substantial reductions in maternal mortality (12), certain serious complications can result after the use of this technique, one of the most significant and serious being epidural hematoma (13). Epidural hematoma, characterized by symptomatic bleeding within the epidural space, may lead to compression, ischemia, nerve trauma, or paralysis.

Impact of Neuraxial Techniques on Bleeding

The epidural space has a rich venous plexus (14) which when injured can bleed, and if this bleeding continues, can potentially lead to peripheral and central neurologic compression. This can then lead to loss of neurologic function if prolonged, and if not relieved, to permanent damage and paralysis (15). The incidence of epidural hematoma is low (∼1:150,000), but the frequency of it occurring increases with impairment of coagulation function along with the type of neuraxial technique that is employed.

Normal Mechanisms to Reduce Bleeding

After injury to any blood vessel, there are three main mechanisms that exist to prevent further bleeding: (i) Vessel wall contraction or spasm (16), (ii) Platelet activation and plugging (17) (Fig. 34-1), and (iii) Intravascular coagulation (18) (Fig. 34-2). Impairment in any of these components could potentially lead to spontaneous (15) or trauma-related epidural hematoma formation (i.e., due to neuraxial anesthesia needle or catheter damage to the epidural vessels) (19).

Blood Vessel Wall

Issues related to a defective blood vessel wall can lead to bleeding in any area of the body. In relation to regional anesthesia and the risk of epidural hematoma formation, the incidence is very low. Clinical conditions with a defective blood vessel wall structure include diseases such as scurvy (vitamin C deficiency) (20) and collagen vascular disease (Marfan’s
syndrome) (21), both of these having been reported as causes of epidural hematoma formation. Overall, defects in blood vessel walls are rare causes of epidural hematoma formation.

Figure 34-1 Formation of a platelet plug at sites of blood vessel damage. Reprinted with permission from: Brass S. Cardiovascular biology: Small cells, big issues. Nature 2001;409:145–147). Copyright © 2001, Rights Managed by Nature Publishing Group.

Platelet Function

Defects related to platelets are a more common cause of concern in obstetric patients, both in relation to quality and quantity of the platelets. Low platelet counts or thrombocytopenia can be defined as a platelet concentration <150,000/mm³ and is common (8%) in obstetric patients (3). Pregnancy-related gestational thrombocytopenia (GTP) is the most common subset of thrombocytopenic obstetric patients (75% of cases); in GTP, the platelet count is low but rarely drops <100,000/mm³ (3). Other common causes of thrombocytopenia in pregnancy result from patients with hypertensive disorders of pregnancy (PIH) (21% of cases), where the platelet counts can drop <100,000/mm³ but usually not <20,000/mm³. The decline in platelet counts may be more precipitous and is largely dependent upon the severity of the disease, e.g., in severe PIH or hemolysis elevated liver enzymes, low platelet counts (HELLP) syndrome (4% to 12% of cases). Less common causes of thrombocytopenia include idiopathic thrombocytopenia (ITP) (4% of cases), where the counts can routinely fall <20,000/mm³ (Table 34-1).

Spontaneous bleeding can result when platelet counts fall <20,000/mm³ and surgical bleeding (or bleeding after vaginal delivery) can occur when counts fall <50,000/mm³. The conventional wisdom was that it was relatively safe to perform neuraxial anesthesia in a patient with a platelet count >100,000/mm³. This data was interpolated from bleeding time studies (22), which have subsequently been shown to be subjective in their assessment, and in addition, may not correlate with the risk of epidural hematoma formation.

Table 34-1 Thrombocytopenia in Pregnancy (3)

Defined as any platelet concentration <150,000/mm³

Gestational thrombocytopenia (GTP) is the most common (75%)
- Platelet count is low but rarely drops <100,000/mm³
Another common cause is pregnancy-induced hypertension (PIH) (21%)
- Platelet counts can drop <100,000/mm³, but rarely <20,000/mm³
Less common cause is idiopathic thrombocytopenia (ITP) (4%)
- Platelet counts can drop <20,000/mm³

Newer Dynamic Coagulation Test Use

While standard coagulation tests currently performed (i.e., PT and PTT) are used frequently to assess the coagulation status of patients, they do not provide information as to the risk assessment of platelet-related bleeding in thrombocytopenic patients. There are more specific tests for platelet function that have been developed such as the thromboelastogram TEG® (Haemoscope Corporation, Niles, IL) and the platelet functional analyzer PFA-100® (Dade-Behring, Dudingen, Switzerland).

The thromboelastogram (TEG) is a viscoelastic test of the whole blood during the coagulation process, which can be used to evaluate the initialization, formation, and strength of clot formation (23). In the standard TEG, a small quantity of blood (0.36 mL) is rotated gently in a cuvette, which is set to mimic sluggish venous blood flow and so activates the coagulation system. This is concurrently followed by sensor rod placement into the blood sample. The strength and speed of clot formation is then measured with the results being quantified graphically. The typical trace can be seen in (Fig. 34-3).

Valuable information is then generated on the activity of the enzymatic coagulation system, platelet function, fibrinolysis, and other factors, which can be related to antithrombotic agents present. TEG has been used since the 1940s (23), but with technical development and improved standardization and reproducibility, it has been used recently in clinical settings at a much greater frequency. TEG is a dynamic test of coagulation, whose maximum amplitude (MA) value is a commonly used clinical variable that correlates to both platelet quantity and function. Sharma presented an elegant paper that showed that the TEG MA values start to become significantly abnormal at platelet counts <75,000/mm³ in patients with preeclampsia (24). This suggested that when a platelet count is seen above this value in preeclamptic patients, it may correlate to the patient having a normal coagulation profile.

While the absolute platelet count is important, its trend over time is equally important in the consideration in assessing the risk/benefit ratio of when to perform a neuraxial regional technique. As an example, if the patient’s platelet count has been stable in the range 75,000 to 80,000/mm³, this would be a more reassuring value to the clinician than a platelet count of 85,000/mm³ if the prior count in that same patient a few hours earlier was substantially >100,000/mm³.

The quality of platelet function is another important clinical factor in determining the bleeding risk after neuraxial block placement. Platelet function in disease states varies. For example, ITP has relatively high functioning platelets (“survival of the fittest”) (25), as compared with conditions such as preeclampsia and von Willebrand disease (26) where platelets may not be as effective.

Once the decision has been made to place a neuraxial block in a parturient with a low but clinically acceptable
platelet count, additional safeguards need to be taken for these patients. These precautions would include utilization of the most atraumatic block needle available (e.g., small 27 gauge spinal needle would be more preferable than a large 17 gauge epidural Tuohy needle), placement by the most experienced provider on the team (not a good candidate for an anesthetic trainee), and extreme vigilance of that patient in the postanesthetic period (e.g., frequent neurologic checks and monitoring).

Figure 34-2 The initiation phase of blood coagulation. Extravascular tissue factor (TF) exposed upon vessel wall injury forms a complex with factor VII/activated factor VII (FVII/FVIIa). Reprinted with permission from: Eilertsen KE, Østerud B. Tissue factor: (patho)physiology and cellular biology. Blood Coagul Fibrinolysis 2004;15(7):521–538.

Figure 34-3 Major TEG parameters. R reflects coagulation factor activities, K and α show fibrinogen and coagula formation. MA indicates platelet function. LY30 reflects fibrinolysis. A30 is the amplitude 30 minutes after MA. Adapted with permission from: Reikvam H, Steien E, Hauge B, et al. Thrombelastography. Transfus Apher Sci 2009;40(2):119–123.

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