MLAB 1227: Coagulation Keri Brophy-Martinez

1. MLAB 1227: CoagulationKeri Brophy-Martinez Coagulation Disorders: Secondary Hemostasis Part One

2. Disorders of the Proteins of Fibrin Formation • Fibrin formation ineffective and slowed so patient presents with abnormal bleeding • Two categories • Inheritance of a defective gene • Failure of synthesis of a hemostatic protein • Malfunction or impaired molecule • Acquired • Acquisition of a deficiency secondary to another condition

3. Terms • Quantitative: amount of a coagulation protein • Qualitative: Present in plasma but functionally defective

4. General Lab Features Lab • PT prolonged • aPTT prolonged • Platelet count normal

5. Clinical Findings Coagulation Factor Disorders Platelet Disorders Bleed from ruptured arterioles Deep muscular & joint bleeding Delayed bleeding Ecchymoses Hematuria No petechiae Bleed from capillaries Superficial bleeding Acute bleeding Ecchymoses Hematuria Petechiae

6. Hereditary Disorders of Secondary Hemostasis • Involve a single factor • Bleeding originates from one site

7. Factor VIII Deficiency • Von Willebrand's Disease – lack of or defective VIII:vWF • Autosomal dominant – seen in both males and females • Most common inherited blood disorder • Platelet abnormalities – adhesiveness and aggregation, bleeding times

8. Von Willebrand's Disease Clinical Features Lab Findings Mild bleeding in mucosal & cutaneous tissues Easy bruising Hallmark is variability of symptoms PTT normal or increased PT normal Platelet count normal BT/ PFA abnormal

9. Factor VIII Deficiency • Hemophilia A – classical hemophilia • Sex-linked recessive • carried by female, manifested in the male • Accounts for 80% of all hemophiliacs • Deficiency of factor VIII portion of VIII/vWf complex • Patient has normal circulating vWf • Abnormal bleeding • Caused by delayed and inadequate fibrin formation • Caused by a secondary increase in fibrinolysis • Failure of TAFI

10. Factor VIII Therapy • Replace clotting factors to achieve hemostasis • DDAVP (desamino-D-vasopressin) • Stimulates storage cells to release VIII and vWF into plasma. • Disadvantage is not all patients can take it

11. Factor IX Deficiency – Hemophilia B, Christmas Disease • <20% of all hemophiliacs • Sex-linked recessive • No Factor IX function • Clinically indistinguishable from hemophilia A, so we see the same disease course

12. Clinical Findings of Hemophilias • Bleeding occurs with NO trauma or trivial injury • Hemarthrosis • Spontaneous bleeding into joints, causes extreme pain and destroys cartilage of knees, elbows, ankles • Deep tissue hemorrhage – internally • Hematuria • CNS bleeding

13. Factor XI Deficiency – Rosenthal's Disease or Hemophilia C • <5% of all hemophiliacs • Autosomal recessive • Highest incidence in Jewish persons of Russian decent • Mucosal bleeding • Requires therapy only following childbirth or surgery

14. Lab Features: Comparison

15. Congenital Disorders of the Other Factors • The following factors are rarely deficient or defective to the extent that coagulation is slowed – I, II, V, VII, X, XII, XIII • Severity of bleeding dependent upon concentration of factor present • PK and HMWK disorders do exist but patients do not have bleeding tendencies.

16. References • McKenzie, Shirlyn B., and J. Lynne. Williams. "Chapter 32." Clinical Laboratory Hematology. Boston: Pearson, 2010. Print.