Coagulation Disorders: Secondary Hemostasis

Part One

MLAB 1227: CoagulationKeri Brophy-Martinez

Disorders of the Proteins of Fibrin FormationFibrin formation ineffective and slowed so

patient presents with abnormal bleedingTwo categories

Inheritance of a defective geneFailure of synthesis of a hemostatic

protein Malfunction or impaired molecule

Acquired Acquisition of a deficiency secondary

to another condition

TermsQuantitative: amount of a coagulation

proteinQualitative: Present in plasma but

functionally defective

General Lab Features Lab

PT prolongedaPTT prolongedPlatelet count normal

Clinical FindingsCoagulation Factor Disorders Platelet DisordersBleed from

ruptured arteriolesDeep muscular &

joint bleedingDelayed bleedingEcchymosesHematuriaNo petechiae

Bleed from capillaries

Superficial bleeding

Acute bleedingEcchymosesHematuriaPetechiae

Hereditary Disorders of Secondary Hemostasis

Involve a single factorBleeding originates from one site

Factor VIII DeficiencyVon Willebrand's Disease – lack of or

defective VIII:vWFAutosomal dominant – seen in both

males and femalesMost common inherited blood disorderPlatelet abnormalities – adhesiveness

and aggregation, bleeding times

Von Willebrand's DiseaseClinical Features Lab FindingsMild bleeding in

mucosal & cutaneous tissues

Easy bruisingHallmark is

variability of symptoms

PTT normal or increased

PT normalPlatelet count

normalBT/ PFA abnormal

Factor VIII DeficiencyHemophilia 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 vWfAbnormal bleeding

Caused by delayed and inadequate fibrin formationCaused by a secondary increase in fibrinolysis

Failure of TAFI

Factor VIII TherapyReplace clotting factors to achieve

hemostasisDDAVP (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 hemophiliacsSex-linked recessiveNo Factor IX functionClinically indistinguishable from hemophilia

A, so we see the same disease course

Clinical Findings of Hemophilias

Bleeding occurs with NO trauma or trivial injury

HemarthrosisSpontaneous bleeding into joints, causes

extreme pain and destroys cartilage of knees, elbows, ankles

Deep tissue hemorrhage – internallyHematuriaCNS bleeding

Factor XI Deficiency – Rosenthal's Disease or Hemophilia C

<5% of all hemophiliacsAutosomal recessiveHighest incidence in Jewish persons of

Russian decentMucosal bleedingRequires therapy only following childbirth

or surgery

Lab Features: ComparisonvWD Factor VIII

DeficiencyFactor IX Deficiency

Platelet count Normal Normal NormalBleeding Time Normal-

increasedNormal Normal

Platelet Function Assay

Normal-increased

Normal Normal

PT Normal Normal NormalPTT Normal-

increasedIncreased Increased

Factor VIII Assay

Normal-decreased

Decreased Normal

Factor IX Assay Normal Normal DecreasedvWF: Ag Assay Decreased Normal Normal

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.