coagulation disorders: secondary hemostasis part one mlab 1227: coagulation keri brophy-martinez
TRANSCRIPT
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
Clinical FindingsCoagulation Factor Disorders Platelet Disorders
Bleed from ruptured arterioles
Deep muscular & joint bleeding
Delayed bleedingEcchymosesHematuriaNo petechiae
Bleed from capillaries
Superficial bleeding
Acute bleedingEcchymosesHematuriaPetechiae
Hereditary Disorders of Secondary Hemostasis
Involve a single factorBleeding originates from one site
Factor VIII Deficiency
Von 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 Disease
Clinical Features Lab Findings
Mild bleeding in mucosal & cutaneous tissues
Easy bruisingHallmark is
variability of symptoms
PTT normal or increased
PT normalPlatelet count
normalBT/ PFA abnormal
Factor VIII Deficiency
Hemophilia A – classical hemophiliaSex-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 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 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 Normal
Bleeding Time Normal-increased
Normal Normal
Platelet Function Assay
Normal-increased
Normal Normal
PT Normal Normal Normal
PTT Normal-increased
Increased Increased
Factor VIII Assay
Normal-decreased
Decreased Normal
Factor IX Assay Normal Normal Decreased
vWF: 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.