24: Management of the Medically Compromised Patient: Hematologic Disorders, Cancer, Hepatitis, and AIDS

CHAPTER 24 Management of the Medically Compromised Patient: Hematologic Disorders, Cancer, Hepatitis, and AIDS

To achieve optimal oral health for the medically compromised patient, the dentist and physician must establish a close working relationship. Because of the complexity of many of these medical conditions additional treatment time may be needed to provide services. To minimize the risk for potential complications that may affect the physical health of medically compromised patients, an aggressive prevention-oriented program is required. Each patient presents a unique set of challenges to the dentist, but achieving a successful outcome can be a rewarding experience. This chapter discusses major medical conditions and their dental management.



The hemophilias are disorders of hemostasis resulting from a deficiency of a procoagulant. Hemophilia is an inherited bleeding disorder affecting approximately 1 in 7500 males.1 Hemophilia A, or classic hemophilia, is a deficiency of factor VIII, also known as antihemophilic factor. Factor VIII deficiency is the most common of the hemophilias and is inherited as an X-linked recessive trait. Therefore males are affected, females are carriers, and there is no male-to-male transmission. If a normal male has children with a carrier of hemophilia, there is a 50% chance that hemophilia will occur in each male offspring and a 50% chance that each female offspring will be a carrier. If a male hemophilic has children with a normal female, all male offspring will be normal, and all female offspring will be carriers. Hemophilia B, or Christmas disease, is caused by a deficiency of factor IX (plasma thromboplastin component) and is also inherited as an X-linked recessive trait. Factor IX deficiency is one-fourth as prevalent as factor VIII deficiency.2,3

Factor XI (plasma thromboplastin antecedent) deficiency, also referred to as hemophilia C or Rosenthal’s’ disease, is inherited as an autosomal recessive trait, with male and female offspring equally affected. This disorder is most frequently observed in those of Ashkenazi Jewish descent. Other factor deficiencies, such as those of factors II, V, and XIII (one case per 1 million population) and factor VII (one case per 500,000 population) are rare and are inherited as autosomal recessive traits.4,5

Von Willebrand disease is a hereditary bleeding disorder resulting from an abnormality of the Von Willebrand factor (VWF) found in plasma, platelets, megakaryocytes, and endothelial cells. VWF circulates in conjunction with factor VIII and is important in platelet adhesion to the subendothelium via collagen and therefore in the formation of the primary platelet plug. In von Willebrand disease, the VWF may have a quantitative or qualitative abnormality. The VWF is composed of subunits called multimers. Von Willebrand disease is divided into subtypes based on the platelet and plasma multimeric VWF structure. Optimal treatment of this disorder is dependent upon the subtype.6

Impaired formation of the platelet plug may result in bleeding from the skin and mucosa, bruising, epistaxis, prolonged bleeding after surgical procedures, and menorrhagia (Fig. 24-1). This is in contrast to hemophilia involving deficiencies of factors VIII and IX, in which the hallmark bleeding events involve muscles and joints (Fig. 24-2).


Hemophilia A (factor VIII deficiency) and hemophilia B (factor IX deficiency) are classified based on the level of the procoagulant present with normal levels ranging from 55% to 100%:

Patients with severe deficiency may experience frequent bleeding episodes, often occurring two to four times per month. Bleeding episodes may be spontaneous, without a specific history of injury or trauma. Common sites of bleeding include joints, muscles, and skin. Hemarthroses (joint hemorrhages) are common, and symptoms include pain, stiffness, and limited motion. Repeated episodes of hemarthroses or muscle hemorrhage result in chronic musculoskeletal disease and culminate in debilitating painful arthritis. Commonly affected joints include knees, elbows, ankles, hips, and shoulders. Pseudotumors (hemorrhagic pseudocysts) may occur in several locations including the jaw, in which case curettage is indicated.7,8

Patients with moderate deficiency experience less frequent bleeding episodes (approximately four to six times per year). However, if a target joint (a joint with repeated episodes of bleeding) develops in a patient with moderate deficiency, spontaneous bleeding may occur. Patients with mild deficiency bleed infrequently and only in association with surgery or injury. The diagnosis of a mild deficiency may occur when an abnormality is found during presurgical evaluation or when bleeding occurs in association with surgery or trauma. The dental care provider may be the first health care provider to identify a patient with mild deficiency as interventions or injury in the oral cavity may unmask a previously undiagnosed individual.

Mouth lacerations are a common cause of bleeding in children with all severities of hemophilia. Sonis and Musselman evaluated 132 patients with factor VIII–deficient hemophilia and noted that “persistent oral bleeding resulted in the diagnosis of 13.6% of all cases of hemophilia.”9 About 29% of cases of mild hemophilia observed were discovered as a result of bleeding from the oral cavity. Of the cases diagnosed secondary to oral bleeding, 78% were the result of bleeding from the maxillary frenum, and 22% resulted from tongue bleeds. Thus initial diagnosis of hemophilia, especially in moderate or mild disease, may directly involve the dentist.


The mainstay of therapy for hemophilia is replacement of the deficient coagulation factor, through the use of purified concentrates either manufactured through recombinant technology or from pooled plasma. In the past, whole blood, plasma, or cryoprecipitate was used for replacement therapy. Factor concentrates are advantageous as they are generally accessible, easily handled and stored, virally inactivated, and commonly result in consistent hemostatic results. The dosage, frequency of administration, and duration of therapy depend on the activity level required, the half-life of the procoagulant, the intervention or procedure contemplated, or the location and severity of the bleeding episode. The half-life of factor VIII is approximately 12 hours, whereas for factor IX it is approximately 18 hours.10

Hemophilia A

Factor VIII concentrate is used for treatment of hemophilia A. Vials of factor concentrate are labeled with the number of international activity units contained, where 1 IU is the amount of activity of the procoagulant present in 1 mL of normal plasma. For routine hemorrhagic episodes, such as early joint, soft tissue, and oral bleeds, a one-time correction to approximately a level of 40% to 50% will achieve hemostasis and resolution of the bleeding episode. For mild factor VIII–deficient hemophilia, DDAVP (1-deamino-8-d-arginine vasopressin) (Sanofi-Aventis, Bridgewater, NJ) may be used for minor hemorrhagic episodes to achieve hemostasis. DDAVP (desmopressin acetate) is a synthetic analogue of the natural pituitary hormone 8-arginine vasopressin (antidiuretic hormone) affecting renal water conservation. This drug, when given intravenously, subcutaneously, or intranasally (Stimate) causes a rise in factor VIII activity and VWF through release from stored sites in endothelial cells, often to the hemostatic range. An appropriate rise in factor VIII activity to hemostatic levels should be documented for any given patient before therapeutic use of this agent, because response may vary among individuals. Peak levels are obtained approximately 1 hour after administration via intravenous and subcutaneous routes and 90 minutes after administration intranasally. The intranasal form of this medication, which is used to treat patients with bleeding disorders, has a more concentrated form of DDAVP compared with the preparation used to treat diabetes insipidus or enuresis. Therefore this preparation should be written for brand name only or in conjunction with the stated concentration of 1.5 mg/mL of desmopressin acetate. Repeated administration of DDAVP may result in tachyphylaxis, a reduction in expected response with sequential dosing due to depletion of storage sites. Use of DDAVP to treat hemorrhagic disorders may also be associated with water retention, hyponatremia, and rarely seizures; therefore monitoring of electrolytes may be required in some circumstances, especially in surgical situations.1113

Hemophilia B

Factor IX–deficient hemophilia is treated with purified coagulation factor IX concentrate (monoclonal and recombinant). In the past, less pure products in the class of prothrombin complex concentrate (PCC) were used. PCCs contained other vitamin K–dependent coagulation factors in addition to factor IX, including some activated forms of these procoagulants. Individuals who require high doses or repeated infusions of PCC are at risk for development of disseminated intravascular coagulation and thrombosis. The minimal desired level for hemostasis is the same for factor IX as for factor VIII (40%). However, the number of units required to achieve that level is different as the volume of distribution of plasma-derived factor IX (1.0) is greater than that for factor VIII (0.5). The volume of distribution of recombinant factor IX is greater than that of plasma-derived factor IX (estimated minimum volume of 1.2 compared with 1, respectively, whereas in infants and young children a minimum volume of distribution of 1.4 should be used for dose calculation). Because interindividual variability of volume of distribution is wide, measurement of activity levels may be required to document a hemostatic level.1417

Clotting factor concentrates are administered in different regimens depending on the patient’s level of severity, number of bleeding episodes, and the treating physician’s recommendations. Treatment regimens may be divided into replacement therapy administered after a bleeding episode has occurred (on-demand therapy) or as administered on a regular scheduled basis to prevent or suppress bleeding episodes (prophylaxis). Prophylactic regimens are further subdivided into primary and secondary. Primary prophylaxis is a long-term treatment for prevention of joint disease instituted before or after minimal hemarthrosis has occurred; secondary prophylaxis may be long or short term, but is instituted after hemarthrosis has occurred or to interrupt a bleeding pattern to rest a joint. Primary prophylactic therapy has been shown in a prospective randomized study to be the most effective regimen to prevent joint disease in patients with severe hemophilia and is now considered the standard of care for these patients.18 Therefore dental care providers should schedule dental evaluations and interventions on regularly planned infusion days, whereas patients treated with on-demand regimens require discussion regarding the need to administer replacement therapy specifically for dental interventions. Patients using regimens of prophylaxis may have a central venous catheter placed due to the need for frequent venous access. The use of antibiotic prophylaxis to protect the central venous access device may be considered although is not recommended by the Centers for Disease Control and Prevention (see Antibiotic Prophylaxis in the section on Dental Management).


Inhibitors are antibodies that neutralize the replaced coagulation factor and are one of the most severe complications for patients. Inhibitors may develop in approximately 28% of patients with severe factor VIII deficiency and in 3% to 5% of patients with severe factor IX deficiency. The key to successful treatment of patients with inhibitors is accurate knowledge of the classification and level of the inhibitor. Patients with inhibitors are divided into two general groups, high responders and low responders, based on the past peak anamnestic response of the inhibitor titer. Inhibitor levels are measured in Bethesda units (BU), a measurement that reflects the ability of the antibody to neutralize a specific amount of procoagulant.23,24

Patients in the low-responding group have peak levels at any time less than 5 BU, and may continue to be treated with factor concentrate, whereas those in the highresponse group have peak titers greater than or equal to 5 BU and require use of bypassing products (either PCC, activated PCC, or recombinant factor VIIa). Hemophilic patients with inhibitors pose considerable treatment challenges and should be managed only in conjunction with a hemophilia-comprehensive treatment center, because hemostasis is often difficult to achieve or maintain.

Other complications of hemophilia include arthritis and degenerative joint disease secondary to recurrent bleeding.25 Blood-borne viral infections represent an important complication of treatment of these disorders and may have been transmitted via required blood or blood products. Hepatitis, including both B and C and resultant liver disease have been a significant source of morbidity and mortality in this patient population.26 The human immunodeficiency virus (HIV) has also been a major source of morbidity and mortality since approximately 1979. Before 1985, there was no antibody test for HIV and no consistent method of viral inactivation in the manufacture of factor concentrates. Therefore between 1979 and 1985, factor concentrates and blood products may have been contaminated with HIV. Approximately 90% of hemophilic patients with severe factor VIII deficiency and 30% of those with severe factor IX deficiency who received factor concentrate during the at-risk period may have become infected with HIV. HIV infection is a sensitive issue to these individuals, who may now bear the burden of two chronic conditions.27 Currently available treatments of factor concentrates made through recombinant technology or pooled plasma have effectively eliminated transmission of HIV and hepatitis B and C. Nevertheless, universal precautions should be followed when treating all hemophilic patients with a history of receiving either factor concentrate.


Antifibrinolytic agents are an adjunctive therapy for dental management of patients with bleeding disorders and are important for prevention or treatment of oral bleeding. These agents include image-aminocaproic acid (Amicar, Xanodyne Pharmaceuticals, Florence, KY) and tranexamic acid (Cyklokapron, Pfizer, New York). Hemophilic patients form loose, friable clots that may be readily dislodged or quickly dissolved, especially in the oral cavity where local fibrinolysis is increased. Antifibrinolytics prevent clot lysis within the oral cavity. They are often used as an adjunct to factor concentrate replacement. For some dental procedures in which minimal bleeding is anticipated, they may be used alone.


Local Anesthesia

In the absence of factor replacement, periodontal ligament (PDL) injections may be used. The anesthetic is administered along the four axial surfaces of the tooth by placement of the needle into the gingival sulcus and the periodontal ligament space. Infiltration anesthesia can generally be administered without pretreatment with either image-aminocaproic acid or replacement therapy. However, if the infiltration injection is into loose connective tissue or a highly vascularized area, then factor concentrate replacement to achieve a level of approximately 30% to 40% activity is recommended.

One must proceed with caution when considering block anesthesia. The loose, connective, nonfibrous, and highly vascularized tissue at the sites of inferior alveolar nerve injection and posterior superior alveolar injections are predisposed to development of a dissecting hematoma, which potentially may cause airway obstruction and create a life-threatening bleeding episode. Therefore a minimum of a 40% factor correction is mandatory with block anesthesia. The dentist must carefully aspirate to ensure that the needle has not entered a blood vessel. If there is bloody aspirate, further factor replacement may be required, and the attending hematologist should be notified immediately following the operative procedure. All patients should be observed for development of a hematoma and immediately referred for treatment in case hematoma forms after the administration of local anesthesia.


Most hemophilic patients can receive outpatient dental care routinely. Appointments should be arranged so that maximum treatment is accomplished per visit to minimize the need for unscheduled factor infusions and hence cost. Patients with inhibitors are best treated at a center with experience in dealing with this complication.3133

The dental procedures used in treating a patient with hemophilia do not differ significantly from those used for unaffected individuals.

Restorative Procedures

The patient with hemophilia should be allowed to consider the prospect of all restorative procedures. Most restorative procedures on primary teeth are successfully completed without factor concentrate replacement using PDL injections of local anesthesia or local infiltration. Small lesions may be restored using nitrous oxide–oxygen inhalation analgesia alone. The use of acetaminophen with codeine may also decrease discomfort in the child.

Most operative procedures for adults may also be completed using local infiltration of anesthetic, a procedure that usually does not require factor concentrate replacement. If a mandibular block or a posterior superior alveolar injection is anticipated, factor concentrate replacement to a level of 40% and antifibrinolytic therapy are required before injection. If factor concentrate replacement is required, all possible restorative treatment should be completed in one visit to minimize the number of infusions required to complete the restorative treatment plan.

A rubber dam should be used to isolate the operating field and to retract and protect the cheeks, lips, and tongue. These soft tissues are highly vascular, and accidental laceration may present a difficult management problem. A thin rubber dam is preferred because there is a decreased tendency to torque the rubber dam retainer and cause gingival tissue abrasion. The retainer should be placed carefully so that it is stable. If a retainer slips, it may lacerate the gingival papilla. Retainers with subgingival extensions should be avoided.

Wedges and matrices can be used conventionally. During proximal preparation, the wedge retracts the papilla, thus protecting it. A properly placed matrix should not cause bleeding.

High-speed vacuum and saliva ejectors must be used with caution so that sublingual hematomas do not occur. Care must also be used in the placement of intraoral radiographic films, particularly in highly vascular sublingual tissues.

The preparation of a tooth for a cast crown requires caution in gingival preparation, as does placement of retraction cord and impression material. Periphery wax is used on the impression tray to prevent possible intraoral laceration during tray placement. Undue trauma should be avoided in cementing or finishing a crown.

Oral Surgery

Preoperative evaluation and postoperative management of the hemophilic patient undergoing extractions must be coordinated with the hematologist. The dentist should discuss with the hematologist the surgical procedure, including the anesthetic technique, the degree of anticipated surgical trauma, and the expected duration for healing. The hematologist can then determine the amount and duration of factor concentrate replacement and adjunctive therapies required for surgery and postoperative management. Today it is possible to perform oral surgery in the hemophilic patient on an outpatient basis.36,37 Requirements include an experienced dentist and hematologist, a facility available for the patient to receive infusions if home infusion is not performed, and a coagulation laboratory capable of timely needed laboratory evaluations. Patients with inhibitors should only be treated in a hospital setting by those experienced in their management.

For simple extractions of erupted permanent teeth and multirooted primary teeth, a 30% to 40% factor correction is administered within 1 hour before dental treatment. Antifibrinolytic therapy should be started immediately before or after the procedure and should be continued for 5 to 10 days. The patient should be placed on a clear liquid diet for the first 72 hours. For the next week, a soft, pureed diet is recommended. During this time, the patient should not use straws, metal utensils, pacifiers, or bottles. After 10 days, the patient may begin to consume a more normal diet. Specific postoperative instructions should be provided to the patient and parent. Factor concentrate is extremely costly, therefore all extractions should be completed in one appointment if possible.

After extractions are completed, the direct topical application of hemostatic agents, such as thrombin or microfibrillar collagen hemostat (Avitene), may assist with local hemostasis. The socket should be packed with an absorbable gelatin sponge (e.g., Gelfoam, Pharmacia and Upjohn Co., Kalamazoo, MI). Microfibrillar collagen or topical thrombin or fibrin glue may then be placed in the wound. Direct pressure with gauze should then be applied to the area.

Stomahesive (J. Knipper and Company, Inc., Lakewood, NJ) may be placed over the wound for additional protection from the oral environment. In general, the use of sutures should be avoided unless suturing is expected to markedly enhance healing, in which case resorbent sutures are recommended. The patient must be given specific and thorough postoperative instructions.

For surgical extractions of impacted, partially erupted, or unerupted teeth, a higher factor activity level may be targeted before surgery. This should be discussed with the hematologist, due to the increased likelihood of surgical trauma and a longer healing period. The hematologist may also elect to administer factor replacement to the patient postoperatively. Antifibrinolytic therapy should be started immediately before or after the procedure and continued for 7 to 10 days.

For simple extractions of single-rooted primary teeth (i.e., incisors and canines), one must evaluate the amount of root development present to determine whether factor replacement therapy is required. If there is complete root development, factor replacement therapy may be required, whereas if there is only partial root formation, antifibrinolytic therapy along with local hemostatic agents may be all that is required.

The normal exfoliation of primary teeth does not usually result in bleeding or require factor replacement. Bleeding in these circumstances can generally be controlled with direct finger and gauze pressure maintained for several minutes. The direct topical application of an adjunctive agent may also help with local hemostasis. If there is continuous slow bleeding, antifibrinolytic therapy may be initiated. In rare circumstances, most commonly when the gingival tissue is repeatedly traumatized during exfoliation, use of factor replacement therapy may be required. In this circumstance, dental evaluation should be performed and consideration given to removal of the exfoliating tooth if repeated trauma cannot be avoided.

Jan 14, 2015 | Posted by in Pedodontics | Comments Off on 24: Management of the Medically Compromised Patient: Hematologic Disorders, Cancer, Hepatitis, and AIDS
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