The most important considerations for maintaining surgical hemostasis begin before the operation starts. This chapter provides practical tools to approach patients before, during, and after the surgical procedure. Below is a summary explanation of normal hemostasis, and how it can be conceptualized into four basic components. Explanations are provided to illustrate the uses and limitations of the routine coagulation tests. Common coagulation disorders are briefly discussed. Preoperative management of anticoagulants is discussed. The routine clinical application of these basic concepts of blood coagulation can enhance practice and benefit patients.
Basic Concepts of Hemostasis
Hemostasis is a term describing the complex processes that keep blood in its fluid state within the vasculature, yet allows it to clot to stop hemorrhage.
The process of normal hemostasis can be divided conceptually into four basic components of the blood, listed as follows: (1) blood vessel, (2) platelets, (3) coagulation system, and (4) fibrinolytic system (Table 5-1).
These four components undergo a series of regulated events that lead to clot formation.
|Blood vessel||Vessel wall; vasoconstriction extravascular proteins, eg, collagen; and tissue factor|
|Platelet||Adhesion, release, aggregation|
|Coagulation system||All coagulation factors, vWF, and natural anticoagulant proteins, eg, protein C, AT-III|
|Fibrinolytic system||Clot lysis, split products|
Four steps leading to a platelet plug formation are as follows:
Blood vessel and platelet interactions
Initial reaction with the blood vessel itself triggering vasoconstriction, which decreases blood flow slowing bleeding and allows for platelet adhesion
The initial contact interaction between platelets and any nonplatelet surface (the vessel wall)
Mediated by a platelet surface glycoprotein receptor termed GPIb complex and the plasma protein, von Willebrand factor (vWF)
A platelet membrane surface receptor, “the aggregation receptor” which is not present on unstimulated platelets is expressed.
The platelet aggregation receptor is made up of two platelet surface proteins, termed GPIIb/GPIIIa.1
GPIIb/GPIIIa binds fibrinogen on one end; another platelet expressing GPIIb/GPIIIa binds the other end of the fibrinogen, leading to platelet aggregation.
Platelets are activated by the adhesion and release of thromboxaine A2, serotonin, and ADP, which activates other platelets, and further slows blood flow.
This whole sequence from vasoconstriction to the formation of a platelet plug and, finally, a platelet aggregate and release constitutes the process of primary hemostasis.
This process is independent of blood coagulation and occurs even in patients with hemophilia.
This process is however insufficient to completely stop hemorrhage—you need adequate secondary hemostasis.
The most common inherited disorder of primary hemostasis is von Willebrand disease and acquired is thrombocytopenia.
Most common bleeding symptoms caused by defects in primary hemostasis are mucosal (epistaxis, hematuria, bleeding gums) and petechial.
After primary hemostasis, a series of interdependent enzyme-mediated reactions initiate the formation of a stable fibrin clot, which replaces the unstable platelet plug.
Secondary hemostasis involves both the intrinsic and extrinsic coagulation cascades.
Tissue factor (TF) is released by the injured endothelium which combines with activated factor FVII (FVIIa) to initiate the extrinsic clotting cascade.2
The exposed collagen and activated platelets (express high molecular weight kininogen (HMK) and prekallikrein (PK)), which allow for the initiation of the intrinsic clotting cascade.
Both pathways intersect at factor Xa and lead to generation of thrombin to form a hemostatic clot.
Most common bleeding symptoms caused by defects in secondary hemostasis are hematomas, hemarthrosis, and hemoperitoneum.
Preoperative Screening: Use of Tests of Coagulation
Preoperative clinical history and examination are the most important components of a preoperative evaluation of the patient’s hemostatic ability.
A careful bleeding history is a more reliable predictor of bleeding than coagulation laboratory tests.
Several retrospective reviews have repeatedly proven that routine coagulation screening tests do not predict bleeding risks in surgical patients, and specifically in patients undergoing tonsillectomy.3
However, considerable variation occurs in the adequacy of a preoperative screening history and examination.
There are three simple questions to remember in taking a bleeding history.
(1) “Have you ever had any surgery?”
Do not forget to ask about dental surgery.
When the patient has undergone a prior surgery without bleeding problems, it serves as a “hemostatic stress test.”
If the patient has had recent major surgery (within 1-2 years) without bleeding, and no active signs or symptoms of bleeding, one can feel confident that the chances of a hemostatic defect are exceedingly small.
(2) “What do you take for pain?”
This is the simplest way to elicit information regarding the patient’s use of non-steroidal anti-inflammatory drugs (NSAIDs) and aspirin (ASA).
Additional uncommon drugs with some hemorrhagic tendency are “garlic,” vitamin E, and fish oil supplements.
(3) “Is there a family history of bleeding or clotting?”
This question obviously hopes to elicit a familial hemostatic defect that has not yet become clinically apparent, or may only emerge in the postoperative setting.
How to Use Screening Tests of Coagulation
If coagulation tests are used, they should be in addition to a careful bleeding history.
The following are the common screening tests of coagulation:
Prothrombin time (PT), activated partial thromboplastin time (aPTT), complete blood count (CBC), and platelet count.
The hemostasis components that coagulation tests measure are listed in Table 5-2.
The PT and aPTT coagulation tests are functional global assays.
These global assays don’t test for specific proteins or enzymes and are, therefore, insufficient measures to assess bleeding risk or assure hemostatic integrity.
Table 5-2 compares screening test to specific components of the hemostatic pathway.
The bleeding time is insensitive to many hereditary disorders, such as von Willebrand disease.
The PT and aPTT are artificial reflections of normal hemostasis, often insensitive.
Some medications, like direct oral anticoagulants, don’t consistently affect these screening tests.
Anticoagulants in Surgical Patients
Understanding anticoagulation in surgical patients is extremely important to prevent and treat postoperative complications, such as thromboembolism. Moreover, this knowledge is critical in patients undergoing surgery who are already on anticoagulants for various reasons.
Heparin is a heterogeneous sugar molecule with molecular weight ranging from 3000 to 30,000 Da.
Heparin is not absorbed orally and must be given intravenously (IV) or subcutaneously (SQ).
About one-third of heparin molecules administered have anticoagulant function.
These heparin molecules act by binding to antithrombin (AT).
UFH also nonspecifically binds to a number of plasma proteins and platelets.
IV dosing has higher bioavailability than SQ.
Nonspecific UFH binding results in variability in anticoagulant response in different patients.
The anticoagulant response to UFH is nonlinear—intensity and duration rise disproportionately with increasing dose.
Four hours is usually sufficient to clear IV heparin (4 × 60 minutes half-life at 100 U/kg).
Dosage of UFH varies based on the indication—treatment or prophylaxis.
Weight-based dosing of UFH is preferred over fixed dosing.
Dosing differs for acute coronary syndrome (ACS) and acute venous thromboembolism (VTE). ACS uses a low-intensity protocol while acute VTE uses a high-intensity protocol.4
Hospitals often have a pharmacy protocol for dosing and laboratory monitoring. These protocols require a bolus dose followed by continuous infusion.
The initial bolus is an IV dose of 60 U/kg (not to exceed 5000 units) followed by 12 to 15 U/kg continuous infusion for low intensity or 18 U/kg continuous infusion for high-intensity regimens.
For ACS an aPTT target therapeutic range is roughly 50 to 70 seconds and for acute VTE target is 60 to 85 seconds. Most hospitals have a measured UFH therapeutic range based on responsiveness of their aPTT reagent to a heparin concentration of 0.3 to 0.7 U/mL (anti-Xa activity) (see following discussion).
Historically, the therapeutic range was set as an aPTT ratio of 1.5 to 2.5 (upper limit of normal) based on retrospective data from the 1970s.
This range resulted in excess heparin exposure and bleeding due to instrument variation.
The current method, each hospital laboratory establishes a therapeutic aPTT range.
This is done with hospital specific aPTT reagent and instruments, simultaneously determining the aPTT (seconds) and heparin concentration (U/mL) using samples from patients receiving UFH for the treatment of thromboembolism. A dose response curve is constructed corresponding to an anti-Xa heparin assay of 0.3 to 0.7 IU/mL.
Prophylaxis dose is generally administered SQ at a dose of 5000 units every 8 or 12 hours.
Prophylaxis dose is not monitored by aPTT, and should not prolong aPTT.
LMWHs are obtained by depolymerization of UFH yielding fragments between 4000 and 5000 Da.
Since the depolymerization yields smaller fragments, the extent of nonspecific binding to plasma proteins and platelets is much less for LMWH than UFH.
The ratio of anti-Xa/anti-IIa activity is more than 4 with LMWH and equal to 1 with UFH.
This small fragment size significantly changes the pharmacology of LMWH.
LMWHs act via AT and potentiate the inhibition of coagulation factors Xa and IIa.
There are several LMWHs including the following:
Danaparoid sodium (Oragaran)
The most commonly used LMWH in the United States is enoxaparin.
Danaparoid, nadroparin, and tinzaparin are not available in the United States.
LMWHs give reproducible anticoagulant effects, therefore they have fixed dosing without monitoring in most patients.
LMWHs do not prolong the aPTT.
Anti-Xa assay can be used to monitor LMWH activity and is recommended
In patients who weigh more than 150 kg
In patients with renal insufficiency
In patients who are pregnant
The anti-Xa activity should be measured 4 hours after the subcutaneous administration with a therapeutic target of 0.6 to 1.0 IU/mL for Enoxaparin.
Other Parenteral Anticoagulants
Fondaparinux (Arixtra) is a synthetic and selective inhibitor of factor Xa.
Fondaparinux is distinctly different from UFH and LMWHs.
It is a synthetic, specific five sugar or pentasaccharide sequence that is responsible for binding to AT.
It does not affect the aPTT, PT, or clotting time, and does not bind to thrombin.
Drug levels can only be monitored by special anti-Xa assays.