Учебники / Otolaryngology - Basic Science and Clinical Review

Surgical hemostasis is described in Schwartz’s Textbook of Surgery as a “complex process that prevents or terminates blood loss from the intravascular space, provides a fibrin network for tissue repair,and ultimately,removes the fibrin when it is no longer needed.” This chapter begins with an overview of the process by way of review and then provides some guidance toward pre-, intra-, and postoperative management of a given patient with a potential bleeding event.

The process of hemostasis begins at the moment of injury to the endothelial lining of the vascular bed. Left undisturbed, the endothelial cells themselves act within a complex series of events to prevent clotting.When the endothelial wall is disrupted, the various elements of the blood are exposed to the underlying collagen.After this initial event, several events rapidly occur to stem the flow of blood from the wound.The first process is that of vasoconstriction at the level of the capillary bed.This process is dependent upon the local contraction of smooth muscle and is influenced by the next event in the cascade of hemostasis; namely, platelet aggregation, as thromboxane A2, a powerful vasoconstrictor, is produced by the release of arachidonic acid from platelet membranes during aggregation.

Within 15 seconds after the onset of vasoconstriction, platelets begin to aggregate as they stick to the exposed collagen.The platelets adhere to the wound bed and begin to form a plug, which is the initial matrix upon which

fibrin will eventually deposit.As the platelets are beginning to aggregate and adhere to the subendothelial collagen, the intrinsic and extrinsic pathways of the coagulation system are also activated by damage to the endothelium, and the two cascades move toward the end point where prothrombin is converted to thrombin, which in turn catalyzes the conversion of fibrinogen to fibrin. Insoluble fibrin is deposited in and around the platelet plug, and a more fully developed clot is formed. At any point on the path from endothelial injury to thrombus formation, a host of factors can derail the process of hemostasis and can produce a potential for prolonged bleeding.

CLINICAL EVALUATION OF A PATIENT FOR POTENTIAL HEMOSTATIC DISORDER

All patients who are scheduled for surgery or who present with an episode of bleeding should be evaluated for a potential occult bleeding disorder. The first and perhaps most sensitive screen to identify a bleeding disorder is the taking of a careful history. A pattern of easy bruising, of prolonged bleeding after minor or major surgery or after tongue biting, of heavy menstrual bleeding, or of any family history of excessive bleeding all warrant further pursuit of an underlying

problem. A history of bleeding disorders such as von Willebrand’s disease and hemophilia should be noted. Any chronic medical problems such as liver or renal disease should be noted, as should any medications that might affect hemostasis (see Tables 1-1 and 1-2).

Once a careful history has been taken, the physical exam should be tailored to identify any hematologic abnormalities. Small telangiectatic lesions on the face, oral or nasal mucous membranes, or fingertips are suggestive of hereditary hemorrhagic telangiectasia; perifollicular skin hemorrhage suggests scurvy, and hemarthrosis in the absence of trauma suggests hemophilia.

LABORATORY EVALUATION

After a careful history and physical examination, the question arises as to what blood tests or further studies

are required to fully assess the patient’s relative risk of bleeding. To some extent, the decision hinges upon both the patient and the extent of surgery that is planned. Patients who are actively bleeding at the time of presentation or who are being scheduled for major surgery routinely require a complete blood count (CBC), a prothrombin time/partial thromboplastin time (PT/PTT), and a full series of blood chemistries, including liver function studies. Further workup based on the history and physical or laboratory abnormalities may merit a hematology consultation for guidance. For patients undergoing more minor procedures, the workup can be tailored by the relative risks of the patient and the surgery itself, although what constitutes “relative” remains broadly interpreted. A good case in point is the debate over what laboratory values are needed prior to performing a tonsillectomy. Although

the American Academy of Otolaryngology–Head and Neck Surgery currently recommends that coagulation studies are warranted only in patients with positive histories or physical examinations, many otolaryngologists do not hold this “standard of care,” even in the face of well-conceived prospective studies.

The following descriptions outline the commonly ordered tests and highlight their clinical importance.

TESTS FOR PLATELET EVALUATION

1.Platelet count

2.Peripheral blood smear

3.Bleeding time

Platelets are 2 m fragments of megakaryocytes that normally number 200,000 to 400,000/mm3. The life span of a platelet ranges from 7 to 9 days. A routine platelet count will give some indication as to the number of circulating platelets. If the platelets are recorded as “clumped,” or if there is some question as to the accuracy of the count, a peripheral blood smear can be performed, and the platelets can be manually counted. In cases where bleeding disorders, such as von Willebrand’s disease, are suspected, a “bleeding time” can provide useful information as to the ability of a patient’s blood to form a clot. Using the Ivy technique, a normal bleeding time averages 5 2 minutes.

TEST OF COAGULATION PATHWAY

The PT/PTT and international normalized ratio (INR) are designed to test the intrinsic and extrinsic cascades, which are part of the coagulation pathway.The PT tests the factors involved in the extrinsic pathway; namely, factors II, VII, IX, and X, which are produced by the liver.The PTT tests the factors in the intrinsic pathway. The INR was introduced because of laboratory variability in reporting the PT. The INR incorporates a correction factor into the PT ratio and standardizes the results. Specific tests for levels of each one of the clotting factors are available and useful in particular cases.

COMMONLY SEEN BLEEDING ABNORMALITIES

PLATELET DISORDERS

Thrombocytopenia is the most common hematologic cause of perioperative bleeding. Thrombocytopenia can arise secondarily to occult disease, megaloblastic anemia (B12 folic acid deficiency), from uremia, from certain

drugs, or from massive blood loss requiring transfusions. Exchange of one blood volume (11 units for a 75 kg male) will result in a decrease in platelet count from 250,000 to 80,000/mm3. Loss of platelets can also be caused by drug allergies or diseases such as idiopathic thrombocytopenic purpura (ITP). As long as the platelet count is 50,000/mm3, there is no absolute need for transfusion. Once the platelet count drops below 40,000/mm3, the risk of spontaneous bleeding increases. The treatment of thrombocytopenia in the nonacute setting begins with an attempt to identify and remedy the causative factor. If the cause is either alcohol or viral related, then the platelet count should return to normal 1 to 3 weeks after the inciting factor has been removed. In the acute setting, where platelets are needed emergently, platelets can be transfused. One unit of pooled platelets usually raises the platelet count by 10,000; therefore, 6 to 8 units are usually required to restore normal clotting.

There are other platelet disorders that do not manifest as thrombocytopenia, but rather are functional disorders (suggested by normal platelet count and increased bleeding time).The most common of these disorders is related to aspirin usage. Aspirin inhibits the entire prostaglandin pathway by irreversibly acetylating cyclooxygenase, which is involved in platelet aggregation. The process is irreversible, so the circulating platelets must be replenished (in a process that takes roughly 72 hours) before they can again function normally. Cephalosporins have also been suggested to cause platelet dysfunction and should be considered a potential cause of bleeding disorders if no other causes are found.

Another common platelet disorder is seen in von Willebrand’s disease; the von Willebrand factor (vWF) normally allows platelets to adhere to the subendothelial system and is responsible for carrying the coagulant portion of factorVIII.When vWF is missing or defective, the ability of platelets to form a plug and begin the process of hemostasis is curtailed. The diagnosis is suggested by a prolonged bleeding time, and treatment may require cryoprecipitate or desmopressin (DDAVP), which causes a transient release of vWF from endothelial cells. This disorder is usually first noted in childhood, and presentation can be variable, depending on the amount of functional vWF. For surgical treatment, vWF should be maintained at 50% of normal.

DISORDERS OF THE

COAGULATION SYSTEM

As with platelets, there are a host of factors that influence and can alter the coagulation system.These include chronic diseases (notably liver disease because factors II, VII,

Exposed Foreign Surface

XII XII(a)

XI XI(a)

IXIX(a)

VIII

calcium

platelet phospholipid

Tissue/Endothelial Damage

Thromboplastin

VII VII(a)

EXTRINSIC CASCADE

Figure 1–1 Overview of intrinsic, extrinsic, and common pathways of hemostasis.Vitamin K–dependent factors are marked with a star (serine proteases). The intrinsic pathway involves the sequential activation of factors XII, XI, and IX (Christmas factor), leading to activation of factorVIII,leading to the activation of the X/V complex of the common pathway (this pathway is tested with the PTT).This

leads to activation of the common pathway in which the X/V complex converts prothrombin (factor II).Thrombin functions to convert fibrinogen to fibrin (factor I), as well as to activate factor XIII, which polymerizes fibrin to form a clot.Thrombin also indirectly activates protein C, which inhibits the X/V complex.

IX, and X are made in the liver), drugs, and massive blood loss followed by transfusion. One of the most common diseases of the coagulation system is an inherited deficiency of one or more of the factors involved in either the intrinsic or extrinsic pathways. Examples of these disorders are hemophilia (deficient for factor VIII) and Christmas disease (deficient for factor IX). Treatment of these disorders acutely may require the administration of fresh frozen plasma.

Another common disorder of the coagulation system is iatrogenic manipulation for purposes of anticoagulation (Fig. 1-1).

The issue of aspirin has been discussed previously because it affects platelet aggregation. Other common medications used to affect the hemostatic system are heparin and warfarin sodium (Coumadin). Heparin is a mucopolysaccharide extracted from the mast cells. It exerts its actions in several ways:by slowing the conversion of prothrombin, by potentiating the effect of antithrombin III, and by decreasing the degree of platelet adhesiveness. It is administered intravenously and has a half-life of 90 minutes. It is monitored by following the PTT level. Due to the short half-life of heparin, discontinuing it several hours before a given procedure should allow the PTT to normalize. More rapid equilibration may require the administration of protamine sulfate.

Warfarin sodium is the oral substitute for heparin. It functions by inhibiting the production of the vitamin K–dependent factors of the coagulation cascade (namely, II, VII, IX, and X). Its half-life is 36 hours. The effects of warfarin sodium can be monitored by following the PT level and the INR. Normalization of the PT and INR can be affected by the administration of fresh frozen plasma.

EVALUATION AND MANAGEMENT OF PERIOPERATIVE BLEEDING

The evaluation of a patient with a bleeding episode, be it on admission to an emergency room or after an operative procedure, depends in its depth on the acuity and severity of the episode. As in all patient management, there needs to be a primary and a secondary survey.The primary survey consists of evaluating the “ABCs” (the airway, breathing, and circulation) and managing the patient accordingly. Once the patient has been stabilized, a more thorough review of the patient can be accomplished. Factors involved in excessive bleeding include ineffective local hemostasis, complications of blood transfusions, hematologic abnormalities, and consumptive coagulopathies.

Control of localized bleeding begins with pressure applied to the area. If there is an identifiable vessel, it can

be ligated or cauterized, or the area can be packed. All packing transmits pressure to the wound bed and provides a scaffold to augment the hemostatic process. Within the realm of otolaryngology, various chemical packing agents are commonly used: these include Gelfoam, Oxycel, Surgicel, and Avitene, among other products. Gelfoam is made from denatured animal skin gelatin. It acts as a pressure matrix; when combined with topical thrombin, a hemostatic effect is produced. Oxycel and Surgicel are cellulose materials that produce a hemostatic effect by their interaction with blood products to form a “clot.” Avitene is microcrystalline collagen that can be helpful with a diffusely oozing wound bed.

When local control cannot be obtained, the decision must be made whether the amount of bleeding warrants surgical exploration and control or whether the difficulty stems from an underlying hematologic problem that needs to be addressed (Fig. 1-2).The laboratory values can be helpful in this regard because they can guide management. If the patient has received massive transfusions, this also must be kept in mind because the patient may require additional factors (i.e., platelets and fresh frozen plasma). If the patient is septic, a consumptive coagulopathy may develop and needs to be treated accordingly by attempting to treat the source of the infection as well as by replacing the various hemostatic factors.

Overall, evaluation and treatment of a patient with either a potential or an active bleeding disorder require some knowledge of the hemostatic process by which the human body repairs itself. Such knowledge allows the development of an algorithim to assess each aspect of this process. Initial management will either quell or temporize the problem; more complicated problems

EndothelialVasoconstriction

Coagulation CascadePlatelet Aggregation

Intrinsic Pathway

Prothrombin Thrombin

Fibrinogen Fibrin Thrombus (Clot)

Figure 1–2 Schematic review of initiation and progression of hemostasis.

merit surgical intervention and the treatment of the underlying hematologic abnormalities.

SUGGESTED READINGS

Bentler E, Lichtman MA, Coller B, Kipps T.Williams Hematology. NewYork: McGraw-Hill; 1995

SELF-TEST QUESTIONS

For each question select the correct answer for the lettered alternatives that follow.To check your answers, see Answers to Self-Tests on page 715.

1.The most common cause of a platelet-related clotting disorder is

A.Idiopathic thrombocytopenic purpura

B.Megaloblastic anemia

C.Von Willebrand’s disease

D.Aspirin therapy

2.Coumadin inhibits the production of which vitamin K–dependent clotting factors?

A.II,V, XIII

B.IV,VII, X

Close HL, Kryzer TC, Nowlin JH, Alving BM. Hemostatic assessment of patients before tonsillectomy: a prospective study. Otolaryngol Head Neck Surg 1994;111(6):733-738

Cohen JR.Vascular Surgery for the House Officer. 2nd ed. Baltimore: Williams and Wilkins; 1992

Schwartz S, ed. Principles of Surgery. New York: McGraw-Hill; 1991

C.II,VII, IX, X

D.II,VII,VIII

3.The best treatment for severe von Willebrand’s disease is

A.Platelet transfusion

B.Protamine infusion

C.Factor VIII infusion

D.Cryoprecipitate