1. MLAB 1227: Coagulation Keri 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 Bleed from ruptured arterioles
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
vWD
Factor VIII Deficiency
Factor IX Deficiency
Platelet count
Normal
Bleeding Time
Normal-increased
Platelet Function Assay PT
PTT
Increased
Factor VIII Assay
Normal-decreased
Decreased
Factor IX Assay
vWF: Ag Assay

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, Print.