Hematologic Disorders

All blood cells play a role in the maintenance of a healthy periodontium. White blood cells (WHCs) are involved in peripheral and inflammatory reactions. Red blood cells (KBC .s) are responsible for g.is exchange and nutrient supply to the periodontal tissues and platelets and are required for normal hemostasis. Disorders of the blood or blood-forming organs can have a prolound effect on the periodontium. Certain oral changes such as hemorrhage may suggest the existence ot a blood disturbance; specific diagnosis, however, requires a complete physical examination and a thorough hematologic study. (Comparable' oral changes occur in more than one form of blood dyscrasia, and secondary inflammatory changes produce a wide range of variation in the oral signs

Cingival and periodontal disturbances associated with blood dyscrasias must be thought of in terms of fundamental interrelationships between Ihe oral tissues and the blood and blood-forming organs rather than in terms of a simple association of dramatic oral changes with hematologic disease. F.cchymosis and petechiae observed most often in the soft palate area is a sign of an underlying bleeding disorder d igs. 12-N and 12-9). Abnormal bleeding from the gingiva or other areas of the oral mucosa that is difficult to control is an important clinical sign suggesting a hematologic disorder. Hemorrhagic tendencies occur when the normal hemostatic mechanisms are disturbed.


I he leukemias arc "malignant neoplasias of YVIU precursors, c haracterized by (11 diffuse replacement of the bone marrow with proliferating leukemic cells; (2) abnormal numbers and forms of immature WB< s in the circulating blood; and (3) widespread infiltrates in the liver, spleen, ■ lymph nodes, and other sites throughout the body."1"8

According to the type of WB( involved, leukemias are classified as lymphocytic or myelocytic; a subgroup of the myelocytic leukemias is monocytic leukemia. According to their evolution, leukemias can be ucute, which is rapidly fatal; subacute; or chronic. In acute leukemia, the primitive "blast" cells are released into the peripheral circulation. whereas in chronic leukemia, the abnormal cells tend to be more mature with normal morphologic charac teristics when released into the circulation.

In till leukemias, the replacement ol the l>one marrow elements by leukemic cells reduces normal production of

RBCs, Witt s, ami platelets, leading to anemia, .1 reduction in the number of nonmalignant Witt s, and thrombocytopenia. Anemia results in poorer tissue oxygenation. making tissues more triable and susceptible to breakdown. A reduction of normal Witt s in the circulation leads to an increased susceptibility to infections. Thrombocytopenia (low platelet counts) leads to bleeding tendency, which can occur in any tissue but has a propensity to occur in the mouth, especially the gingival sulcus dig. 12-10). Some patients may have normal blood counts while leukemic cells are present in the bone marrow; this type ol disease is called aleukemic leukemia.m

The Periodontium in Leukemic Patients

Oral and periodontal manifestations of leukemia consist of leukemic infiltration, bleeding, oral ulcerations, and infections.

Leukemia Bleeding
Fig. 12-8 Petechiae evident on the soil palate ol patient with underlying bleeding disorder

Leukemic Infiltration of the Periodontium,

Leukemic cells can infiltrate the gingiva and, less frequently, the alveolar bone. Gingival infiltration often results in leukemic ^in^ival enlargement (see ( hap-m IS).

A study ot 1076 adult patients with leukemia showed that 3.6% of the patients with teeth had leukemic gingival proliferative lesions, with the highest incidence in patients with acute monocytic leukemia (66.7%), followed by acute myelocytic-monocytic leukemia (IK.7%) and acute myelocytic leukemia (3.7%).VI It should be pointed out, however, that monocytic leukemia is an extremely rare form of the disease. Leukemic gingival enlargement is not found in edentulous patients or in patients with chronic leukemia. Leukemic gingival enlargement consists of a basic infiltration of the gingival curium In leukemic cells that creates gingival pockets where bacterial plaque accumulates, initiating a secondary inflammatory lesion that contributes also to the enlargement ol the gingiva.

Clinically, the gingiva appears initially bluish red and cyanotic, with a rounding and tenseness of the gingival margin; then it increases in size, most often in the interdental papilla and partially covering the c rowns of the teeth (Figs. 12-11, 12-12, and 12-13).

Microscopically, the gingiva exhibits a dense, diffuse infiltration of predominantly immature leukocytes in the attached and marginal gingiva. Occasional mitotic figures indicative of ectopic hematopoiesis may be seen. I :ie normal connective tissue components of the gingiva are displaced by the leukemic cells (Pig. 12-14, A). I he nature of the cells depends on the type of leukemia. I he cellular ac cumulation is denser in the entire reticular connective tissue layer. In almost all cases, Ihe papillary layer contains comparatively few leukocytes. I he blood vessels are distended and contain predominantly leukemic cells, and the RIKN are reduced in number. I he epithelium presents a variety of changes. It may be thinned or hyperplastic. Common findings include degeneration associated with intercellular and intracellular edema and leukocyl c infiltration with diminished surface keratiriization.

The microscopic picture of the marginal gingiva differs from that of the remainder of the gingiva in that it usually exhibits a notable inflammatory component, in

Tonsillar Pillar Cancer
Fig. 12-9 Ecchymosis evident on the lateral aspects ol the soil palate and tonsillar pillars of patient with chemotherapy induced thrombocytopenia.
Buccal Sulcus Ecchymosis
Fig. 12-10 Spontaneous bleeding trom the gingival sulcus in a patient with thrombocytopenia. Normal coagulation is evident by the large clot that forms in the mouth However, platelets are inadequate to establish hemostasia

216 I'AR I l lii'Iogy <>l l\'ri<iilonhtl l)is«iscs

Localized Gingival Swelling

Fig. 12-11 Leukemic infiltration causing localized gingival swelling ol ihe interdental papilla

Hematologic Disorders

Fig. 12 13 Acute myelocytic leukemia. A, View of patient's face. Note the elevated flat macules and papules (leukemia cutis) on the right cheek B, Intraoral view showing the pronounced gingival enlargement C, Occlusal view ol upper anterior teeth. Note the marked enlargement in both the facial and the palatal aspects. (Courtesy Dr. Spencer Woolfe, Dublin, Ireland.)

Fig. 12-11 Leukemic infiltration causing localized gingival swelling ol ihe interdental papilla

Fig. 12-12 Acute lymphocytic leukemia. The gingiva Is Inflamed, edematous, and discolored and bleeds spontaneously

Fig. 12 13 Acute myelocytic leukemia. A, View of patient's face. Note the elevated flat macules and papules (leukemia cutis) on the right cheek B, Intraoral view showing the pronounced gingival enlargement C, Occlusal view ol upper anterior teeth. Note the marked enlargement in both the facial and the palatal aspects. (Courtesy Dr. Spencer Woolfe, Dublin, Ireland.)

addition to the leukemic cells. Scattered foci of plasma cells and lymphocytes with edema and degeneration arc common findings. Ihe inner aspect of the marginal gingiva is usually ulcerated, and marginal necrosis with pseudomembrane formation may also be seen.

The periodontal ligament and alveolar bone may also he involved in acute and subacute leukemia (see lig. 12-14, It). The periodontal ligament may he infiltrated with mature and immature leukocytes. Ihe marrow of the alveolar bone exhibits a variety ol changes, such tis localized areas of necrosis, thrombosis of the blood vessels, infiltration with mature and immature leukocytes, occasional RB(\ and replacement of the fatty marrow by fibrous tissue.

In leukemic mice, the presence of infiltrate in marrow spaces and the periodontal ligament results m osteo porosis ol the alveolar bone with destruction ol the supporting bone and disappearance of the periodontal fibers tlig. 12-15}.*" 40

Ihe abnormal accumulation of leukemic cells in the dermal and subcutaneous connective tissue is called leukcmiu cutis and forms elevated flat macules and papules I see lig. 12-U, A).^ *™

Bleeding. Gingival hemorrhage is a common finding in leukemic patients (see l ig. 12-10), even in the absence ol clinically detectable gingivitis. Bleeding gingiva tan be an earls sign of leukemia.,so It is due to the thrombocytopenia that results from replacement of the bone marrow cells by leukemic cells and also from the inhibition of normal stem cell function by leukemic cells or their products.1'*

Human Autopsy
Fig. 12-14 A, Leukemic infiltrate in gingiva and bone in a human autopsy specimen. B, Same cave as in A. Note the dense infiltrate in marrow spaces and the lack ol extension to the periodontal ligament.

This bleeding tendency can also manifest itself in the skin and throughout the oral mucosa, where petechial* are often found, with or without leukemic infiltrates. Oral bleeding has been reported as a presenting sign in 17.7% of patients with acute leukemia and in 4.4% of patients with chronic leukemia.1Js I his symptom can also result from the chemotherapeutic agents used.

Oral Ulceration and Infection. Ihe granulocytopenia resulting from the replacement of bone marrow cells by leukemic cells reduces the tissue resistance to opportunistic mic roorganisms and leads to ulcerations and infections. Discrete, punched-out ulcers penetrating deeply into the submucosa and covered by a firmly attached white slough can be found in the oral mucosa.11 These lesions occur in sites of trauma such «is the buccal mucosa in relation to the line of occlusion or the palate. Patients with past history of herpes infection may develop herpetic oral ulcers, often in multiple sites and large atypical forms and after chemotherapy is instituted8* (Fig. 12-16).

(lingival bacterial infection in leukemic patients can be a primary bacterial infection or result from an increased severity of existing gingival or periodontal disease. Acute gingivitis and lesions of necrotizing ulcerative gingivitis are more frequent and severe in terminal cases of acute leukemia19 (Figs. 12-17 and 12-18).

In leukemia, the response to irritation is altered so that the cellular component of the inflammatory exudate differs both quantitatively and qualitatively from that which occurs in nonlcukcmic individuals. There is pronounced infiltration of immature leukemic cells in addition to the usual inflammatory cells.

The inflamed gingiva differs clinically from inllamed gingiva in nonlcukeinic individuals. It is a peculiar bluish red, is markedly spongelike and friable, and bleeds

Periodontal Ligament Components
Fig. 12-15 Leukemic infiltrate in alveolar bono in leukemic mouse. Note the leukemic infiltrate producing destruction ol bone and loss of periodontal ligament.

persistently on the slightest provocation or even sponta-neouslv. I bis markedly altered and degenerated tissue is extremety susceptible b> bacterial inlection. which can be so severe as to cause acule gingival necrosis and pseudomembrane formal ion (l igs. 12-19 and 12-20). Ilíese are secondarv oral changes superimposec! on the

2IS PARI ■ tobbgyvt lh'rWilonta!l)tsi'iiscs

Palate Necrosis
Fig. 12-16 Large ulcerations on the palate ol patient with granulocytopenia secondary to leukemia These atypical ulcerations are caused by herpes virus opportunistic infection. Notice the smaller, discrete round ulcerations that have coalesced into Ihe larger lesion
Granulocytopenia Associated Gingivitis
Fig. 12-17 A, Anterior view o patient with acute myelocytic leukemia. Interdental papilla are necrotic with a highly inflamed and swollen base B, Palatal view demonstrating extensive necrosis ol interdental and palatal tissue.
Step Ladder Effect Interdental Bone

Fig. 12-18 Same patient as in Fig 12-17 following chemotherapy and initial induction of remission A, Anterior view reveals that although the tissue health has dramatically improved, the interdental papilla have been lost. B, Palatal view shows extensive loss of gingival tissue around maxillary incisors.

Fig. 12-18 Same patient as in Fig 12-17 following chemotherapy and initial induction of remission A, Anterior view reveals that although the tissue health has dramatically improved, the interdental papilla have been lost. B, Palatal view shows extensive loss of gingival tissue around maxillary incisors.

oral tissues altered by the blood disturbance, l'hey produce associated disturbances that may be a source ol considerable difficulty to the patient, such as systemic-toxic effects, loss of appetite, nausea, blood loss from persistent gingival bleeding, and constant gnawing pain. By eliminating local factors, it is possible to alleviate severe oral changes in leukemia.

Chronic Leukemia

In chronic leukemia, clinical oral changes suggesting a hematologic disturbance are very rare. I he microscopic changes in chronic leukemia may consist of replacing the normal fatty marrow of the jaws with islands of mature lymphocytes or lymphocytic infiltration of the marginal gingiva without dramatic clinical manifestations.

The existence of leukemia is sometimes revealed by a gingival biopsy performed to clarify the nature of a troublesome gingival condition. In such cases, the gingival findings must be corroborated by medical examination and hematologic study. The absence of leukemic involvement in a gingival biopsy specimen does not rule out the possibility of leukemia, in chronic leukemia, the gingiva may simply present inflammatory changes, with no suggestion of a hematologic disturbance. In patients with recognized leukemia, the gingival biopsy indicates the extent to which leukemic infiltration is responsible for the altered clinical appearance Of the gingiva. . I/-though such findings are of interest, their benefit hi the patient is insufficient to warrant routine gingival biopsy studies ill patients with leukemia.


Anemia is a deficiency in the quantity or quality of the blood as manifested by a reduction in the number of erythrocytes and in the amount of hemoglobin. Anemia may be the result of blood loss, defective blood formation, or increased blood destruction.

Anemias are classified according to cellular morphology and hemoglobin content as I) macrocytic hyper-

Necrotic Pseudomembrane
Fig. 12-19 Opportunistic bacterial infection of the gingiva in a patient with leukemia. Gingival tissue is highly inflamed, bleeding and necrotic with pseudomembrane formation.

chromic anemia (pernicious anemia); 2) microcytic hypochromic anemia (iron deficiency anemia); sickle cell anemia; or 4) normocylic-normochroniic anemia (hemolytic or aplastic anemia).

Pernicious anemia results in tongue changes in 75% of cases. The tongue appears red, smooth, and shiny, owing to atrophy of the papillae. I here is also marked pallor of the gingiva d igs. 12-21 and 12-22).

Iron deficiency anemia induces similar tongue and gingival changes. A syndrome consisting ol glossitis and ulceration of the oral mucosa and oropharynx, inducing dysphagia (Plummer-Vinson syndrome), has been described in patients with iron deficient') anemia.

Sickle cell anemia is a hereditary form of chronic hemolytic anemia that occurs almost exclusively in blac ks. It is characterized by pallor, jaundice, weakness, rheumatoid manifestations, and leg ulcers. Oral changes include generalized osteoporosis of the jaws, with a peculiar stepladder alignment of the trabeculae of the interdental septa, along with pallor and yellowish discoloration of the oral mucosa. Periodontal infections may precipitate sickle cell crisis.1"'

Sickle Cell Crisis
Fig. 12-20 The opportunistic bacterial infection in this immuno suppressed patient caused complete destruction of the gingiva exposing the underlying alveolar bone.
Sickle Cell Anemia Trabecula Photo
Fig. 12-21 Diffuse pallor of the gingiva in a patient with anemia The discolored, inflamed gingival margin stands out in sharp contrast to the adjacent pale, attached gingiva

Aplastic anemias result from a failure of the hone marrow to produce erythrocytes. Their etiology is usually the effect ol toxic drugs on the marrow. Oral changes include pale discoloration of the oral mucosa and increased susceptibility to infection, owing to the concomitant neutropenia.


Thrombocytopenic purpura may be idiopathic (i.e., of unknown etiology, as in VVerlhof's disease), or it may occur secondary to some known etiologic factor responsible lor a reduc tion in the amount of functioning marrow and a resultant reduction in the number of circulating platelets. Such etiologic factors include aplasia of the marrow; crowding out of the megakaryocytes in the marrow, as in leukemia; replacement of the marrow by tumor; and destruction of the marrow by irradiation or radium or by drugs such as benzene, aminopyrine, and arsenical agents.

Thrombocytopenic purpura is characterized by a low platelet count, a prolonged clot retraction and bleeding

Thrombocytopenic Purpura Tongue
Fig. 12-22 Smooth tongue in a patient with pernicious anemia.

time, and a normal or slightly prolonged clotting time. There is spontaneous bleeding into the skin or from mucous membranes. Petechial* and hemorrhagic vesicles occur in the oral cavity, particularly in the palate, tonsillar pillars, and the buccal mucosa (see I igs. 12-8 and 12-9). Hie gingivae are swollen, sttft, and friable, Weeding (m ars spontaneously or on the slightest provocation and is difficult to control. (jingival changes represent iin abnormal response to load irritation; the severity of the gingival condition is dramatically alleviated by removal of the local factors (Tig. 12-23).

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  • marian
    Which condition is responsible for hematologic gingival disease?
    6 years ago
  • mark johnson
    Does the sickle cell anemia affect the periodontium?
    6 years ago
  • amaranth
    What is diffuse slough of marginal gingivae?
    6 years ago
  • omar senay
    How to get cure of hematological disease?
    8 months ago

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