The diagnosis and treatment of bleeding tendencies

The diagnosis and treatment of bleeding tendencies A brief Donald Boston,

review Leake, Mass.

D.M.D.,

M.D.,*

and Daniel

Deykin,

M.D.,**

The basis of treatment of bleeding diatheses is accurate diagnosis. Diagnosis begins with a complete medical history. Once the possibility of a disorder is raised by either the patient or his family or by the physician or dentist, appropriate steps to diagnose the disorder should be undertaken. With the correct diagnosis, the dentist undertaking the patient’s care will be better prepared not only to prevent bleeding but also to cope with it when it does occur.

E

xtracting a tooth is a provocative challenge to the hemostatic system. Failure to achieve hemostasis after tooth extra&ion is often the first clue to an unsuspected bleeding diathesis, especially if the defect is mild. In order to avoid postoperative bleeding, the best therapy begins with prevention. A careful history provides clues and is more useful than the results of any single laboratory test in evaluating a potential bleeding problem. In fact, a history of bleeding is more significant than the absence of a coagulation defect in the usual screening tests. When a disorder is known, treatment is usually specific and straightforward. When it is only suspected, on the basis of the history, a standard series of laboratory evaluations will elicit most disorders. Specific assays may then characterize the disorder, and appropriate therapy may be begun prior to surgery. NORMAL HEMOSTASIS

The trigger that initiates the hemostatic process is injury to the vascular endothelium. As a result of the injury, two events take place simultaneously: *Associate in Oral Surgery, .Children% Hospital Medical Center, Boston, Mass. at present, Chief of Oral Surgery, Harbor General Hospital, Torrance, Calif., and Associate Professor of Surgery, Division of Oral Surgery, University of California at Los Angeles. **Director, Hemostasis Units, Beth Israel Hospital and the Children’s Hospital Medical Center, Boston, Mass.; Associate Professor of Medicine, Harvard Medical School.

852

Volume 32 Number 6

Diagnosis cot lagen endolhrlium

and treatment

of bleeding tendencies a53

I. VESSEL DISRUPTION a. Constriction b. Exposure of collagen

2. PLATELET REACTIONS WITH COLLAGEN a. Swelling, degranulation b. Release of ADPand other contents

3. PLATELET REACTIONS WITH ADP a. Loore aggregailon, morphology intact, reverri ble Pig. 1. Primary hemostasis-temporary hemostatic plug. Figs. 1 to 4 are from Deykin, D.: Thrombogenesis, Beth Israel Hospital Seminars in Medicine, edited by Feingold and Hiatt, published by Little, Brown and Company, 1969. (Reprinted with permission.)

vascular constriction occurs and a temporary hemostatic plug forms. Blood platelets in the area of injury adhere to the subendothelial collagen fibers exposed by disruption of the endothelium. Platelet-collagen contact alters the platelet. The platelets are attracted to the collagen and adhere to it. Once absorbed on collagen, platelets swell and degranulate, which releases many of their intracellular constituents into the ambient bloodstream. Among the components released are serotonin, which may enhance the vascular constriction already initiated by injury, and the nucleotide, adenosine diphosphate (ADP) . The released ADP causes aggregation of other platelets, more ADP is released, and a self-perpetuating cycle is established as the plug forms. The events described thus far comprise primary hemostasis, shown in Fig. 1. This platelet plug in a contracted vessel is the first barrier to loss of blood. At this point the hemostatic plug is a loose, reversible aggregate of platelets. That this reaction is essentially independent of the blood-clotting mechanism should be emphasized. It is normal in persons with hemophilia, and it is completely unaffected by anticoagulants currently employed in clinical medicine. The second phase of hemostasis, in which prothrombin is converted to thrombin, involves the transformation of the temporary hemostatic plug formed by the loose platelet aggregates into a permanent plug (Fig. 2). This transformation is brought about by the activation of the blood-clotting mechanism, which is initiated at the same time as primary hemostasis by disruption of the endothelium and exposure of the underlying collagen to blood. There are two major pathways by which prothrombin is converted to thrombin. These are the so-called intrinsic and extrinsic pathways. When the

854

Leake

Oral Burg. December, 1971

and Deykin

I.

2. INTRINSIC

EXTRINSIC

COAGULATION

COAGULATION

SYSTEM

SYSTEM 3.

VESSEL

Releaseof

tissue

b.

Exposure

of

ACTIVATION

Extrinsic

b.

Intrinsic

-

T PL collagen

EVOLUTION

o.

Fibrin

b.

Platelet

swelling,

releose

reaction

DEFIN

I TIVE a.

thromboplostin

collagen

OF COAGULATlON

o.

THROMBIN

I THROMBIN

4.

DISRUPTION

O.

Flbrln

formotion degronulotlon,

HEMOSTASIS , platelet

nidus

Fig. d. Secondary hemostaais.

endothelial barrier is broken by vascular injury, tissue thromboplastin is released into the ambient blood, thereby initiating a series of reactions by which thrombin is evolved via the extrinsic pathway. At the same time, collagen fibers are exposed, and they activate factor XII, or the Hageman factor, thereby initiating the intrinsic scheme of the blood-coagulation mechanism. As a result of activation of both of these pathways, thrombin is evolved from prothrombin. In the presence of thrombin, the mass of loosely aggregated intact platelets (aggregation is caused by adenosine diphosphate) is transformed into a densely packed mass of platelets whose architecture is no longer discernible. This aggregate, now bound together by strands of fibrin formed about it, is no longer reversible. It thereby forms a definitive hemostatic barrier against loss of blood. All the factors required by the intrinsic system are present in the circulating blood. The extrinsic system, which overlaps the intrinsic system, depends on tissue thromboplastin (factor III), a lipoprotein, which is released by the injured cells. The intrinsic system is sometimes shown as a progression of events occurring in cascade fashion, whereby inert precursors are transformed into active forms which activate the next factor in the clotting scheme. After the activation of factor XII, the cascade continues by other linked reactions of factors XI (plasma thromboplastin antecedent or PTA), factor IX (plasma thromboplastin component, PTC), factor VIII (antihemophilic globulin, AHG) , and factor X (the Stuart factor). In the extrinsic system, factor X is activated directly by thromboplastin, factor VII (convertin), and calcium. Just as in the intrinsic system, activated factor X promotes the conversion of prothrombin to thrombin, which activates fibrinogen to form fibrin. The loose fibrin polymer formed in this reaction is converted into the tight fibrin polymer by conversion of hydrogen bonds to

Diagnosis

Volume 32 Number 6

and treatment

tendencies

855

I I

I I

I I I I

I I I I I’

“I

of bleeding

, PROTHROMBIN I I I I I

9 --

x /

Tissue

m

I

Y

I Lipid I I

TPL

I I I I I I I I

I

Fig. 3. The coagulation

v

THROMBIN--;-

I I I I 1 I t I

FIBRIN

(Loose)

xlu 1 FIBRIN

(Tight)

mechanism (schematic).

covalent bonds. This reaction is mediated by active factor XIII, which was itself activated by thrombin. (See Fig. 3.) Thus, thrombin plays two major roles: It is responsible for (1) the consolidation phase of the platelet plug and (2) the conversion of fibrinogen to fibrin. Fibrin then replaces the platelet aggregate over a period of hours to days. In summary, as platelets progressively adhere to denuded subendothelial collagen at the site of injury and to each other, they undergo fusion as a platelet plug develops. As fibrin forms, a fibrin-platelet meshwork develops which is the definitive hemostatic plug. The over-all reaction is shown schematically in Fig. 4. CAUSESOF BLEEDING

It is widely held that the most common cause of postoperative bleeding is failure to suture adequately. This is often true of postextraction bleeding, but extraction sites may also bleed for prolonged periods because of too vigorous rinsing or spitting and failure to apply adequate pressure on the bleeding site. Simple extractions may require nothing more than firm pressure, and even multiple extractions in children often require only pressure. Abnormal bleeding may be due to a variety of causes : too few platelets (thrombocytopenia) , poor platelet function (thrombasthenia) , or inherited or acquired coagulation defects. PLATELETPROBLEMS

Platelets in adequate numbers and of good quality are essential for primary hemostasis. Platelet deficiency is the most common cause of abnormal bleeding and exhibits a wide range from mild to very severe bleeding. Clinical bleeding

856

Leake

Oral Surg. Deaember, 1971

and Deykin VESSEL

1

I*HEMOSTATlC

INJURY

I 1

CONTRACTION

I

WALL I

COLLAGEN

/v PLATELET REACTIONS

TISSUE

ACTIVATION COAGULATION

1

TPL

OF

PLUS LWTtN6

REACll@JM

Fig. 4. The normal hemostatic sequence.

with platelet deficiencies consists principally of purpura and bleeding from mucous membranes. Abnormal bleeding is rare if the platelet count is above 60,000 per cubic millimeter. However, there is no clear-cut threshold below which bleeding will always occur. Patients with counts as low as 10,000 per cubic millimeter may have negative histories of bleeding. Thrombocytopenia is nearly always acquired. It may be due to a variety of causes, often definable, or it may be idiopathic. Disorders of production of platelets include hypoproliferative disorders wherein the marrow is depressed, as it is secondary to irradiation, chemical or drug suppression, or replacement of the marrow by neoplastic cells, and certain anemias, notably vitamin Blz and folk acid deficiencies. Other causes of thrombocytopenia include increased destruction of platelets, as in immune reaction secondary to drugs and in lupus erythematosus, and idiopathic autoimmune platelet destruction. Intravascular coagulation occurs in the microcirculation in a variety of conditions in which platelets and coagulation factors are consumed; hence the term consumptive couguZopatky. A list of the conditions includes large cavernous hemangiomas; neoplasms, such as carcinoma of the prostate, ovary, pancreas, or cardiac bypass surgery; and gramstomach, etc. ; obstetrical complications; negative septicemia. Widespread vasculitis produces thrombocytopenia due to direct consumption of platelets by damaged subendothelial collagen, as in patients with thrombotic thrombocytopenic purpura, prosthetic cardiovascular devices, or by toxic, metabolic, or immunologic vasculitis. Idiopathic thrombocytopenic purpura (ITP) is one of the most common forms of thromboeytopenia and may arise at any age, Although it is commonly seen in children and young adults as a self-limiting disease, its course in older adults may be insidious and unremitting. The onset of ITP may be abrupt. Sometimes the first sign of bleeding follows an operation.

Volume 32 Number 6

Diagnosis

and treatment

of bleeding

tendencies

857

Thromb&henia is a qualitative disorder of platelets in which the platelet count is normal but bleeding time is prolonged. The platelets are 10~ in ADP. They do not adhere to collagen. Blood clots fail to contract. The platelet constituent that is deficient is a contractile protein called “thrombasthenin.” Thrombopathy is a term used to describe another functional disorder of platelets, one in which there is defective aggregation presumably due to inadequate activation of a phospholipid with procoagulant activity, designated his platelet factor 3. Patients with impaired activity of platelet, factor 3 may have or because of an a bleeding defect because of low levels, “deficit thrombopathy,” inability to release platelet factor 3, “functional thrombopathy.” Defective release of platelet factor 3 may occur in patients with uremia, liver disease, scurvy, and the dysproteinemias. It has been reported in normal newborn infants, and in persons with myelofibrosis, multiple myeloma, pernicious anemia, chronic lymphatic leukemia, and systemic lupus erythematosus. COAGULATION DEFECTS

Hereditary defects are usually single. The deficiency is of only one factor, and the defect persists at a constant level throughout life. This defect varies from person to person but is usually constant in any one family. The clinical severity is related to the degree of deficiency. The concentration of the deficient factor may range from a trace to 60 per cent. Patients with more than 25 per cent of a factor may not bleed unless challenged by trauma, The first notice of the defect may come in a dental office. Coagulopathies that occur most frequently are hemophilia, deficiency of either factor VIII or factor IX inherited as sex-linked recessive characteristics, and von Willebrand’s disease, inherited as an autosomal trait, presumably dominant. The frequency of factor VIII deficiency is about 60 to 80 per million; of factor IX deficiency, 15 to 20 per million. These diagnoses may become more common as diagnostic techniques now used detect more patients with deficiencies. Other known coagulation factor defects include deficiencies of factors I, II, V, VII, X, XI, and XIII, all of which are inherited as autosomal recessive traits and whose frequencies of occurrence are from less than 0.5 to about 1.0 per million. There is no clinical syndrome with a deficiency of factor III (thromboplastin) , factor IV (calcium), or factor XII (Hageman). Acquired defects are usually multiple and are secondary to an underlying disorder. In liver disease, notably cirrhosis, factors V and the prothrombin group (factors II, VII, IX, and X) are most depressed in production. Malabsorption, as in sprue, pancreatic, or biliary disease, may promote deficiency of vitamin K and thus depress the production of the prothrombin group of factors. Coumarin, used therapeutically to induce hypocoagulability, is a ~mpetit,ive inhibitor of vitamin K and similarly depresses the prothrombin group. Factor VII is depressed initially, followed by depression of factors IX, X, and II. The return of factor levels to normal requires 10 days to 2 weeks if vitamin K is not

858

Leake

Table I.

and Deykin

Oral Ikccmber,

A glossary of coagulation factorsnomenolatwe

Coagulation

interwtional

nomenclature Synmyms

Defioienoy

state

I

Fibrinogen

Afibrinogenemia

II

Prothrombin

Hypoprothrombinemia aprothrombinemia

III

Thromboplastin

-

IV

Calcium

-

V

Proaecelerin Labile factor Ac-globulin

VII

SPCA Convertin Stable factor

VIII

Antihemophilic (AH(J) Antihemophilic Antihemophilic

IX

globulin

Classic

factor factor

(AHF) A

Plasma thromboplastin ponent (FTC) Antihemophilic factor

com-

Stuart factor (Stuart-Prower)

XI

Plasma thromboplastin antecedent (PTA)

XIII

or

Parahemophilia

x

XII

Surg. 1971

Hageman factor Antihemophilic factor Fibrin stabilizing factor (FW La&-Lorand factor

B

hemophilia

Hemophilia

A

Christmas

disease

Hemophilia

B -

Hemophilia D -

given additionally. If vitamin K is given, the levels begin to rise within 2 hours and attain the maximum in 48 hours. It is not definitely established that long-term antibiotic therapy depresses the prothrombin group. INHIBITOR

FORMATION

The problem of inhibitors, circulating anticoagulants, complicates operations. Inhibitors occur in a variety of clinical situations. They may arise after transfusions, presumably on a specific antigen-antibody basis. In the presence of inhibitors, the addition of normal plasma or cryoprecipitates is ineffective in correcting the abnormal clotting times. Anticoagulants have been described for factors VIII, IX, V, XI, fibrinogen, and XIII, although those for factors V, XI, and XIII are very rare. The presence of an anticoagulant for factor X in lupus erythematosus is well recognized. Inhibitors may be tested by mixing or diluting the patient’s plasma with that of a normal patient. Dilutioort of clotting factors and pZateZets during and after massive rapid transfusion (eight or more units of banked blood) may result in a major bleed-

Volume Number

Diagnosis

32 6

Table II.

and treatment

of bleeding tendencies

Distinguishing features of hemophilioid and purpuric states

Bleeding

source

Lesion Preceding

Usually

small

artery

Often intramuscular hematomas trauma

Frequent

Purpuras

states

Hentophilioid

(delayed

Usually deep onset)

capillary

Cutaneous petechiae

and mucosal and/or ecchymoses

Unusual

Venipuncture

No superficial ecchymoses, but massive hemorrhage may occur if firm pressure not held long enough

Superficial ecchymoses venipuncture site

Transmission

Sex-linked in about cases

No sex-linked hereditary

Sex Bleeding Tourniquet

859

Rare time test

hereditary history 40 per cent of

in females

More

common

Normal

Usually

Negative

Frequently

around

history in females

prolonged positive

ing problem. The shelf-life of factors V and VIII and of platelets is short compared to that of other factors. Blood stored at 4O C. for more than 24 hours is uselessin replacing platelets and should not be used in the case of deficiencies of factor V or factor VIII. However, platelets specifically separated in satellite bags and stored at room temperature may be useful for up to 72 hours. EVALUATION OF THE PATIENT The history taken from the patient or parents provides the most useful clues in discovering bleeding diatheses preoperatively. The patient with no past history of bleeding should be questioned specifically about response to trauma, previous operations, and dental extractions. The history should emphasize such symptoms as easeof bruising, character of menses, gingival bleeding, epistaxis. The aim is to define the category of bleeding (that is, purpuric or primary defect, coagulation or seconda.ry defect) and to establish the etiology. If, on the basis of the history, there is any question of a bleeding tendency, a careful evaluation of the patient should be completed prior to the operation. This should include a complete physical examination, examination of a stained smear of peripheral blood, and any other appropriate hematologic studies. The patient with a past history of excessive bleeding should be questioned about the age at onset, the severity of the symptoms, and the characteristics of bleeding. A defect of primary hemostasis, usually manifested by immediate onset and by involvement of the mucous membranes or skin, suggests platelet abnormalities or a vascular component, such as telangiectasis. Secondary bleeding defects, caused by deficiencies of coagulation factors, are characterized by delayed onset after trauma and typically involve deep tissues or joints. In recording a family history of bleeding, one should note the number of relatives with bleeding tendencies, the severity of such bleeding, and the relationship to the patient. Maternal uncles, grandfather, or male cousins with bleeding problems suggest sex-linked recessive inheritance, as in hemophilia.

860

Leake and Deylkin.

Oral December,

Surg. 1971

The physical examination includes an evaluation of the location and type of active or recent bleeding and a search for signs of earlier bleeding, such as range of movement of joints which may be diminished from hemarthrosis or muscle contractions. Neurologic disturbances, such as femoral nerve paralysis or loss of sensation, may be the sequelae of bleeding. Other signs may include those of anemia, splenomegaly, lymphadenopathy, hepatomegaly, abdominal masses, or bone tenderness. Changes in the tongue may suggest amyloidosis or pernicious anemia. Large hemangiomas may suggest thrombocytopenia,. Signs of liver disease include spider angiomas, palmar erythema, hepatosplenomegaly, and jaundice. Urine and feces should be examined for occult blood. Purpuric areas on the trunk and extremities may provide clues. The bruises of thrombocytopenia are usually small, rarely more than 5 cm. across. Massive bruises are common in hemophilia and rare in other conditions. LABORATORY

EXAMINATION

There is a plethora of laboratory examinations for the evaluation of bleeding disorders. The aim in choosing laboratory studies is to make an accurate and rapid, yet economical diagnosis of the bleeding problem. After the history and physical examination, a stained film or smear of the peripheral blood is studied. In a wide variety of diseases, characteristic changes occur in the number and proportions of cells that comprise the peripheral blood. These changes generally reflect alterations in the rate of formation of the various cells in blood-forming organs. This provides useful information in making the diagnosis and in following the response to therapy. Routine tests to evalute clotting are bleeding time, prothrombin time, activated partial thromboplastin test, thrombin time, whole clot retraction and lysis, and platelet evaluation-number and function (by aggregometry with collagen, ADP, and epinephrine) . Specific assays for each of the coagulation factors are carried out as indicated. Bleeding

time

Bleeding time evaluates blood vessel components and reflects the primary plug formation which is affected by a diminished platelet count or by an abnormal platelet function. A modification of the Ivy method is used. A blood pressure cuff is applied to the arm at approximately 40 mm. Hg of pressure. The forearm is prepared with an alcohol sponge, and a Bard-Parker No. 11 blade is used to make three discrete puncture wounds, each about 2 mm. in depth and 1 to 2 cm. apart. The edges of the wounds are blotted with filter paper at 30-second intervals, with care being taken to avoid the wound itself. Normal bleeding time is less than 8 minutes. Prothrombin

time

The onestage prothrombin time screens the extrinsic system, which is comprised of tissue thromboplastin (factor III), factors VII, X, V, and II,

Diagnosis

and treatment

of bleeding

tendencies

861

fibrinogen (factor I), and calcium. Principle-Tissue thromboplastin is added to plasma and the mixture is recalcified. The clotting time is compared to normal, which is 12 to 14 seconds. A deficiency of any of the above-mentioned factors, as well as the presence of inhibitors, will prolong the clotting time. Activated

partial

thromboplastin

test

This test measures intrinsic activation as well as prothrombin and fibrinogen. Principle-A platelet substitute (crude phospholipid) is added to plasma. The mixture is recalcified, and the clotting time is noted. Not only the above-mentioned factors but inhibitors also prolong clotting time. Kaolin is added to activate factors XII and XI maximally thus reducing the error which the surface of the tube introduces. Thrombin

time

Thrombin time measures the third clotting phase. Principle-Thrombin is added to the patient’s plasma, and the time of coagulation of fibrinogen is measured and compared to normal. Normal clotting time is approximately 10 seconds, depending on the amount of thrombin added. Abnormalities of thrombin time are found with deficiencies of fibrinogen or inhibitors of thrombin (for example, heparin) . Whole

blood

clotting

time

Whole blood is allowed to coagulate, and the time required for the firm clot to form is noted. This measures the whole coagulation sequence except for factor VII. It may be normal in mild defects, but is prolonged in severe defects. Whole

blood

clot lysis time

Whole blood is allowed to clot, and the time required is recorded (normal is over 48 hours).

for the clot to lyse

ANTICOAGULANTS

Anticoagulants are used therapeutically in a variety of clinical states associated with embolic thrombotic phenomena. Patients receiving anticoagulants may bleed profusely after dental operation unless proper precautions are taken. Heparin is used in acute states. It is given intravenously, and its action is immediate, direct, and proportional to its level in the blood. Heparin’s effect is to block the activation of factor IX by XI, and to block the thrombin conversion of fibrinogen to a fibrin monomer. Heparin is metabolized in the liver. Its clearance from plasma varies; the half life ranges from 1 to 21/2 hours. Toxic effects: The major problem is bleeding. Long-term therapy may produce metabolic bone disease. Rarely, thrombocytopenia may result. The formation of aldosterone is also blocked. Heparin’s activity is monitored by either whole blood clotting time or by activated partial thromboplastin time. The antidote for heparin is protamine.

862

Leake

and Deykin

Oral December,

Burg. 1971

Coum&~ are given by mouth; the half life varies from 15 to 60 hours. The mode of action is inhibition of vitamin K-dependent synthesis of factors VII, IX, X, and II. The coumarins are bound loosely to plasma albumin and are degraded by the liver. Toxicity includes bleeding and occasionally skin necrosis. Control is by the one-stage prothrombin time. The result is usually reported as the percentage of normal: Do not extract a tooth when the value is under 25 per cent. The antidote to the coumarins is vitamin K given orally or parenterally. Plasma may be used. Patient

management

Some guidelines for routine care of the patient with bleeding diatheses are as follows: Most operative work may be done with a rubber dam in place. If the dam is carefully placed, there is no trauma to the patient, and it is protective, for example, against a flying broken burr. Infiltration anesthesia usually suffices for most operative procedures. Mandibular blocks should never be used. They are absolutely contraindicated because of the possibility of bleeding into the submandibular and subglottic areas and into the mediastinum, thereby obstructing the airway. Chemical cautery or electrosurgery should be avoided because of tissue necrosis with secondary hemorrhage. This is particularly true of patients with coagulation defects. Surgical technique is emphasized. Bony fragments and granulation tissue should be carefully removed when extractions are performed. Where there is bleeding from specific points in the alveolar bone, the use of bone wax or crushing of the bone may be necessary. Even though it should be stressed that there is no substitute for replacement of deficient factors, local measures should also be used to control bleeding from any accessible site. Pressure applied to the point of bleeding is always indicated in oral bleeding. Topical hemostatic agents should be used. Bovine thrombin or Russell’s viper venom are useful, with the exception that thrombin is not effective in the case of aflbrinoginemia, in which a clot does not form, and Russell’s viper venom is useless in patients deficient in Stuart factor X, upon which it reacts. Superficial clots should be removed to expose the actual bleeding point. Gelfoam or Oxycel or gauze soaked in thrombin or Russell’s viper venom can then be applied with pressure to the wound. Multiple extraction sites do not require suturing when a splint has been carefully placed. However, if no splint is used, multiple extraction sites should be gently sutured to keep the gingiva apposed to the alveolar bone. Nonabsorbable sutures on an atraumatic needle are used. Absorbable sutures are not recommended because they promote the formation of granulation tissue and delay healing. Therapy is based on establishing and maintaining the minimum concentration of a clotting factor necessary for effective hemostasis. Replacement of the deficient factor is dependent on the survival time (that is, the biologic half life of the factor) as well as the shelf-life or storage stability of the factor.

Volume 32 Number 6

Diagqtosis and treatment

of bleeding

tendencies

863

All the coagulation factors, with the exception of factors V and VIII, are O C. and will survive for several weeks as 4 quite stable during storage at banked blood or plasma. Factors V and VIII are quite labile and must be given as fresh plasma or whole blood, or as frozen or lyophilized fresh plasma. Factor VIII can now be given in concentrated form, as a cryoprecipitate which allows a concentration ten times greater than that of whole plasma. In therapy, there is an iriitial rate of disappearance much greater than that accounted for by metabolic turnover. For this reason, the initial loading dose should be relatively greater than that required for maintenance. Risk

Although transfusion therapy for bleeding diatheses may be life saving, there are, nonetheless, risks inherent in transfusion of blood or plasma products. These include febrile and allergic reactions, complications of overloading the circulation, incompatibility reactions, thrombophlebitis, air and fat emboli, and the transmission of infections-malaria, syphilis, and especially hepatitis. The risk of hepatitis increases as the number of units used increases. Pooled commercial concentrates have a notably high risk associated with transfusion. Other complications include hypocalcemia and/or hyperkalemia in massive or exchange transfusion. Acute renal failure may be a consequence of a hemolytic transfusion reaction. AHG

deficiency

By far, the most common inherited bleeding problem faced by the dentist is that of classic hemophilia. The AHG level aimed for is 20 to 30 per cent of normal. Most hospitals now have available commercially prepared concentrates of AHG. Cryoprecipitate is given in an initial dose of 1.0 unit per 10 kilograms of body weight 1 hour before surgery, followed by a maintenance dose of 0.7 units per 10 kilograms of body weight. For other factors, the minimal level for surgery is as follows : 1. AHG (VIII), 20 to 30 per cent of normal; short half life. Use cryoprecipitate. 2. PTC (IX), 15 to 25 per cent; use banked blood or plasma; 60 ml. of plasma per kilogram initially, and then 7 ml. per kilogram every 12 hours for 10 to 14 days or use a concentrate. 3. Fibrinogen (I), half life 4 to 5 days; concentration low (50 mg./ 100 ml.) ; use plasma or fibrinogen. 4. Prothrombin (II), congenital deficiency very rare; level required for hemostasis about 40 per cent; use crude concentrate containing factors VII, X, II, and IX. 5. Proaccelerin (V), 15 to 30 per cent; treat with fresh frozen plasma, 10 to 15 ml. per kilogram of body weight; short half life: 14 to 30 hours. 6. Convertin (VII), 4- to B-hour half life very short; need 5 per cent level of normal for effective hemostasis; give plasma 5 to 10 ml. per

864

Leake

7.

8.

9. 10.

and Deykin

Oral Burg. December, 1971

kilogram on day of operation, then 5 ml. per kilogram for 3 to 5 days. Stuart (X), 16 hours half life; concentration 15 per cent for dental extractions; give 15 ml. of plasma per kilogram, followed by 10 ml. per kilogram 3 to 5 days. PTA (XI), long half life of 60 to 65 hours; banked blood or plasma 10 ml. per kilogram of body weight several hours prior to surgery; maintenance 5 ml. per kilogram for 5 to 7 days. Hageman (XII), not a clinical problem in spite of effect on in vitro coagulation tests. FSF (XIII), treat with plasma; long half life.

SUMMARY

The basis of treatment of bleeding diatheses is accurate diagnosis. begins with a complete medical history. Once the possibility of a raised by either the patient or his family or by the physician appropriate steps to diagnose the disorder should be undertaken. correct diagnosis, the dentist undertaking the patient’s care will be pared not only to prevent bleeding but also to cope with it when it

Diagnosis disorder is or dentist, With the better predoes occur.

REFERENCES

1. Ashford, T. P., and Freiman, D. G.: The Role of the Endothelium in the Initial Phases of Thrombosis, Am. J. Pathol. 59: 257, 1967. 2. Ashford. T. P., and Freiman. D. cf.: The Role of the Intrinsic Fibrinolvtic System in the Prgention’of Stasis Thrombosis in Small Veins, Am. J. Pathol. 5$: Ill?, 1968. 3. Ashford, T. P., and Freiman, D. G.: Platelet Aggregation at Sites of Minimal Endothelial Injury, Am. J. Pathol. 58: 599, 1968. 4. Schulman, I.: Vascular Factors in Hemostasis, Annu. Rev. Med. 14: 339, 1962. 5. Holmsen, J., Day, H. J., and Stormorken, H.: The Blood Platelet Release Reaction, &and. J. Haematol., Suppl. No. 8, pp. l-26, 1969. 6. Marcus, A. J.: Platelet Function, N. Engl. J. Med. 280: 1213, 1278, 1330, 1969. 7. Spa&, T. H., and Zucker, M. D.: Mechanism of Platelet Plug Formation and Role of Adenosine Diphospate, Am. J. Physiol. 266: 1267, 1964. 8. Ratnoff, 0. D.: The Biology and Pathology of the Initial Stages of Blood Coagulation, Progr. Hematol. 6: 204, 1966. 9. Davie, E. W., and Ratnoff, 0. D.: Waterfall Sequence for Intrinsic Blood Clotting, Science 145: 1312, 1964. 10. Gaston, L. W.: The Blood Clotting Factors, N. Engl. J. Med. 270: 236, 290, 1964. 11. Deykin, D.: Thrombogenesis, N. Engl. J. Med. 276: 622, 1967. 12. Pechet, L.: Fibrinolysis, N. Engl. J. Med. 273: 996, 1024, 1965. 13. Udall, J. A.: Human Sources and absorption of Vitamin K in Relation to Anticoagulation Stability, J. A. M. A. 194: 127, 1965. 14. Biggs, R., and MacFarlane, R. G.: Human Blood Coagulation, ed. 3, Oxford, 1962, Blackwell Scientific Publications. 15. Hougie, C.: Fundamentals of Blood Coagulation in Clinical Medicine, New York, 1963, McGraw-Hill Book Co., Inc. 16. Ratnoff, 0. D., editor.: Treatment of Hemorrhagic Disorders, New York, 1968, Hoeber Medical Division, Harper and Row. 17. Salzman, E. W., and Britten, A.: Hemorrhage and Thrombosis. A practical Guide, Boston, 1965, Little, Brown & Co.

Reprint reqbests

to:

Dr. Donald Leake Chief, Division of Oral Surgery Harbor General Hospital 1000 Weat Carson St. Torrance, Calif. 90599