Extrinsic

Also assesses common pathway

Factors II, VII, IX, and X

Protein C and S

Factors II, VII, IX, and X

Protein C and S

Factors II, V, X, VIII, IX, XI, and XII

High molecular weight kinnogen

Prekallikrein

Fibrinogen

Intrinsic

Also assesses common pathway

Warfarin

Heparin

Factor VIII

Factor IX

• Ecchymoses
• Hemarthrosis
• Muscle hemorrhage
• Excessive bleeding with surgery
• Joint pain, swelling, erythema
• Decreased range of motion
• Swelling
• Pain with motion of affected muscle
• Signs of nerve compression
• Potential life-threatening blood loss
• Bleeding with dental extractions or trauma
• Genitourinary bleeding
• Hematuria
• Intracrantial hemorrhage

• Prolonged aPTT
• Decreased factor VIII/factor IX level
• Normal PT
• Normal platelet count
• Normal vWF antigen and activity

• Routine immunizations + Hep A and B
• Perinatal care of male infants of hemophilia carriers
• DOC: IV factor replacement

• Not from donors
• Risk of transmiting infection is low
• No hepatitis or HIV ever reported --> HOWEVER parvovirus B19 has been reported
• Efficacy comparable to plasma derived factor VIII

• Potential to transmit infection
• No cases of HIV transmission since 1986
• Hep C has been reported
• Hep A outbreaks reported
• Parvovirus reported

• Half life of infused factor
• Patient's body weight
• Vd
• Presence and titer of inhibitory antibody to factor VIII

• Facial flushing
• HA
• Tachycardia
• Hypotension
• Water retention/hyponatremia

Conduct a desmopressin trial

there must be at least a twofold rise in factor VIII (minimum 0.3 units/ml) within 60 min after giving desmopressin

Aminocaproic acid

Tranexamic acid

• High purity
• Excellent efficacy in the control of bleeding
• Excellent viral safety profile
• Low risk of thromboembolic complications

Thrombotic complications

• DVT
• PE
• MI
• DIC

• High or repeated doses
• Liver disease
• Neonates
• Crush injuries/surgery

2-3x usual replacement dose of factor

OR

More frequent dosing intervals

• PCCs
• Activated PCCs
• Recombinant activated factor VII
• Porcine factor VIII (alternative)

• Recombinant factor VIIa and PPCs have failed
• Hemorrhages are severe

Immune Tolerance Therapy

• Scheduled infusion of high doses of factor

Adjunctive Immunomodulatory Therapy

• Cyclophosphamide
• Prednisone
• IV Immune Globulin

Rituximab

• Anti-CD20 monoclonal antibody
• Used in a few patients with factor VIII inhibitor
• MOA: rapid depletion of circulating B cells that produce antibodies

• Surgical intervention
• Intensive physical therapy
• Intra-articular dexamethasone injection
• Mild pain -- acetaminophen
• Severe pain --- narcotics

• Most common
• Mild to moderate reduction in vWF and factor VIII
• Inheritance is autosomal dominant with variable penetrance and expression
• Bleeding symptoms vary from mild to moderate

• Qualitative abnormality of vWF
• Inheritance typically autosomal dominant, but may be recessive
• Bleeding symptoms may be more severe than type 1

• Severe quantitative variant
• vWF nearly undetectable and factor VIII levels very low
• Inheritance is often autosomal recessive

• vWF normal
• Defect in the platelet glycoprotein Ib receptor that causes increased affinity for normal vWF

• Rare bleeding disorder similar to congenital form
• vWF normal, but removed rapidly by anti-vWF antibodies, adsorption to tumor cells, or other mechanisms

Associated with:

Autoimmune Disorders

• Systemic lupus erythematosus
• Lymphoproliferative disorders
• Neoplastic disease

Medications

• Valproic acid
• Dextran
• Ciprofloxacin

• PT normal
• aPTT prolonged if factor VIII is decreased
• Bleeding time is normal to prolonged
• Platelet count is normal, however decreased with type 2B and platelet type pseudo-vWD

• Most with Type 1
• Some with Type 2A

• Bleeding, Thrombosis, or both
• Petechiae and purpura
• Peripheral cyanosis
• Hemorrhagic bullae

• Poor nutrition
• Broad spectrum antibiotics
• Diseases (CF, Crohn's, Ulcerative colitis, cholestatic liver disease, celiac disease, amyloidosis, Whipple's, short-bowel syndrome)

• Phytonadione

PO

SQ

IM (avoid in pts with severe hypoprothrombinemia)

IV (restricted to pts with thrombocytopenia or unable to absorb)