MLAB 1227: Coagulation Keri Brophy-Martinez Coagulation Disorders: Secondary Hemostasis Part One

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

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

General Lab Features Lab PT prolonged aPTT prolonged Platelet count normal

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

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

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

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

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

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

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

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

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

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

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.

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