Dental Management in Hematologic Disorders

Coagulation factors and related substances

Number and/or name I (fibrinogen) II (prothrombin) III Tissue factor IV Calcium Function Forms clot (fibrin) Associated genetic disorders Congenital afibrinogenemia, Familial renal amyloidosis

Its active form (IIa) activates I, V, VII, VIII, Prothrombin G20210A, Thrombophilia XI, XIII, protein C, platelets Co-factor of VIIa (formerly known as factor III) Required for coagulation factors to bind to phospholipid (formerly known as factor IV) Co-factor of X with which it forms the prothrombinase complex Unassigned old name of Factor Va Activates IX, X Co-factor of IX with which it forms the tenase complex Activates X: forms tenase complex with factor VIII Activates II: forms prothrombinase complex with factor V Activates IX Activates factor XI, VII and prekallikrein Crosslinks fibrin congenital proconvertin/factor VII deficiency Haemophilia A Haemophilia B Congenital Factor X deficiency Haemophilia C Hereditary angioedema type III Congenital Factor XIIIa/b deficiency Activated protein C resistance

V (proaccelerin, labile factor) VI VII (stable factor, proconvertin) VIII (Antihemophilic factor A) IX (Antihemophilic factor B or Christmas factor) X (Stuart-Prower factor) XI (plasma thromboplastin antecedent) XII (Hageman factor) XIII (fibrin-stabilizing factor)

von Willebrand factor

prekallikrein (Fletcher factor) high-molecular-weight kininogen (HMWK) (Fitzgerald factor) fibronectin antithrombin III heparin cofactor II protein C protein S

Binds to VIII, mediates platelet adhesion

von Willebrand disease

Activates XII and prekallikrein; cleaves Prekallikrein/Fletcher Factor deficiency HMWK Supports reciprocal activation of XII, XI, and Kininogen deficiency prekallikrein Mediates cell adhesion Inhibits IIa, Xa, and other proteases Inhibits IIa, cofactor for heparin and dermatan sulfate ("minor antithrombin") Inactivates Va and VIIIa Cofactor for activated protein C (APC, inactive when bound to C4b-binding protein) Mediates thrombin adhesion to phospholipids and stimulates degradation of factor X by ZPI Degrades factors X (in presence of protein Z) and XI (independently) Converts to plasmin, lyses fibrin and other proteins Inhibits plasmin Activates plasminogen Activates plasminogen Inactivates tPA & urokinase (placental PAI) Pathological factor X activator linked to thrombosis in cancer Glomerulopathy with fibronectin deposits Antithrombin III deficiency Heparin cofactor II deficiency Protein C deficiency Protein S deficiency

protein Z Protein Z-related protease inhibitor (ZPI) plasminogen alpha 2-antiplasmin tissue plasminogen activator (tPA) urokinase

Protein Z deficiency

Plasminogen deficiency, type I (ligneous conjunctivitis) Antiplasmin deficiency Familial hyperfibrinolysis and thrombophilia Quebec platelet disorder

plasminogen activator inhibitor-1 (PAI1)

plasminogen activator inhibitor-2 (PAI2) cancer procoagulant

Inactivates tPA & urokinase (endothelial PAI) Plasminogen activator inhibitor-1 deficiency

Dental management of bleeding disorders

Replacement therapy : 1. platelet concentrate : thrombocytopenia ( 1 unit= 30,000/ uL enough for 1 day ) 2. Fresh frozen plasma : liver disease, Hemophilia B, vWD type III 3. Factor VIII,IX concentrate : Hemophilia A ( 1 unit /kg can add 2%, so 50 unit /kg add 100% ) 4. Factor IX concentrate : Hemophilia B 5. 1-desamino-8-darginine vesopressin (DDAVP) : Hemophilia A, vWD type I, II

Antifibrinolytic therapy: 1. E-aminocaproic acid (EACA, Plaslloid) 2. Tranexamic acid (AMCA, Transamin)

Factor Replacement Therapy

The basic treatment to stop or prevent bleeding in people with hemophilia A and B is factor replacement therapy. This is the infusion (injection into the bloodstream) of factor VIII and IX concentrates to prevent or control bleeding.

These concentrates come from two sources: human plasma (a component of blood) or a genetically engineered cell line made by DNA technology, called recombinant.

Local hemostatic methods

splints, pressure packs, sutures; gelfoam with thrombin, surgicel, oxycel, microfibrillar collagen(avitene), topical AHF

Heparin (anticoagulant)
Complex inhibited ( IXa, Xa, XIa, XIIa ) Used in deep vein thrombosis , renal dialysis Rapid onset, Duration 4-6hrs ( given IV ) Monitoring by aPTT: 50-65 sec Discontinue 6 hrs before surgery then reinstituting therapy 612hrs post op Protamine sulfate can reverse the effect

Coumarin (Vit k antagonist)

Inhibit Vit K action (Factor II,VII,IX,X) Used venous thrombosis, cerebrovascular disease Duration half-life 40hrs Monitored by PT : INR 1.5-2.5 PT>2.5, reduction coumarin dosage ( 2-3 days ) Vit. K can reverse the effect

Aspirin (antiplatelet)
Inhibit cycloxygenase, TxA2 formation Analgesic drug impairs platelet function Aterial thrombosis, MI Tests-BT, aPTT If tests are abnormal , MD should be consulted before dental surgery is done Stop aspirin for 5 days, substitute alternative drug in consultation with MD

A decrease in number of circulation platelets Idiopathic thrombocytopenia, secondary thrombocytopenia TX : is none indicated unless platelets<20000/mm3, or excessive bleeding TX : Steroid, platelet transfusion

THROMBOCYTOPENIA

Gene mutation on Von Willebrands factor; most common Inherited disease in America ( 1% ) Type I : 70%-80%, partial loss on quantity Type II : poor on quality Type III : severe loss on quantity, inactive to DDAVP

VON WILLEBRANDS DISEASE

Clinical Features
At around 6 months, child develop bruises and hamarthrosis as he starts to move around. Normal level of factor VIII is 50%-150%, and severity is measured according to this level: 1. severe: <1% F VIII or IX: liable for spontaneous hamarthrosis & muscle hematoma 2. Moderate : 1-5% F VIII or IX: mild trauma or surgery causes hematoma 3. mild: 6-50% F VIII or IX: major surgery or injury results in excess bleeding.

Clinical Features
Joints commonly affected include: knees, elbows, ankles, and hips. They look hot, swollen, and very painful and tender With recurrent bleeding there will be synovial hypertrophy, destruction of cartilage and secondary osteoarthritis, In muscles : calf, psoas: bleeding lead to ischemia, necrosis, fibrosis which will lead to contracture & shortening of tendons e.g achilles tendon making walking difficult.

Hemophilia A is a deficiency of factor VIII and hemophilia B (Christmas disease) is a deficiency of factor IX. Hemophilia is considered severe when plasma activity is <1 IU/dL (normal range 50-100); moderate if it ranges between 2 and 5 IU/dL, and mild if it is between 6 and 40 IU/dL.

HEMOPHILIA

Dental Management
General Avoid any mucosal injuries by: Careful use of saliva ejectors; Careful removal of impressions; Care in the placement of X-ray films, particularly in the sublingual region; Protection of soft tissues during restorative treatment by using a rubber dam or applying yellow soft paraffin (vaseline).

Dental Management
Preventive dentistry 1. tooth brushing, flossing, rubber cup prophylaxis & topical fluoride, supragingival scaling 2. without prior replacement therapy

Anesthesia and pain management 1. minor analgesic such as paracetamol (acetaminophen). 2. Avoid aspirin, NSAIDs

Dental Management
Anesthesia and pain management
LOCAL ANESTHETIC TECHNIQUES NO HEMOSTATIC COVER REQUIRED Buccal infiltration Intra-papillary injections Intraligamentary injections HEMOSTATIC COVER REQUIRED Inferior dental block Lingual infiltration

Dental Management
Orthodontic treatment : 1. no contraindication in well-motivated patients 2. care with placement of bands and wires

Operative dentistry 1. rubber dam to protect tissue against accidental laceration 2. wedges should be place to protect and retract papilla

Dental Management
Pulp therapy 1. Preferable to extraction 2. Avoid over instrumentation and overfilling

Periodontal therapy 1. no contraindication of probing and supragingival scaling 2. deep scaling, curettage, surgery need replacement therapy

Dental Management
Oral surgery : 1. Dental extraction: 40%-50% level 2. Maxillofacial surgery (including surgery extraction of impaction teeth): 80-100% 3. Antifribrinolytic therapy & local hemostatic measure Tranexamic acid (usual adult dose 1 g three times a day) and epsilon aminocaproic acid (EACA) (50 mg/kg four times a day), are the most commonly used drugs. They should be continued for a total of 7 days. 4. Do not open lingual tissue in lower molar regions to avoid hemorrhage track down a endangered airway 5. Always carry out treatment as atraumatically as possible

Dental Management
Peri-operative period Have the patient rinse with chlorhexidine mouthwash for 2 minutes before the administration of the local anesthetic. Suture the socket if the gingival margins do not oppose well. use of oxidized cellulose or fibrin glue if indicated Use a soft vacuum formed splint to protect the socket if needed.

Dental Management
Postoperative instructions: No mouth rinsing for 24 hours; No smoking for 24 hours; Soft diet for 24 hours; No strenuous activities for 24 hours; Prescribed medication must be taken as instructed; Analgesia should be prescribed for use if required; Salt-water mouthwashes (1 teaspoon of salt in a glass of warm water) should be used four times a day starting the day after the extraction for 7 days Antibacterial mouthwash may be used; Emergency contact details must be given to the patient in case of problems.