Coagulation Disorders: Primary vs Secondary Hemostasis

• Disorders of coagulation are divided into primary hemostasis (platelet/vascular problems) and secondary hemostasis (coagulation factor problems).

Primary Hemostasis

• Onset is spontaneous bleeding, immediately after trauma.
• Affects skin and mucous membranes.
• Forms petechiae and ecchymosis in the superficial layers of the skin.
• Mucous membrane involvement is common in nasal, oral, GIT, and GUT areas.
• Clinical examples include thrombocytopenia, platelet defects (adhesion, aggregation & release), Von Willebrand disease, and scurvy.

Secondary Hemostasis

• Onset is delayed after trauma.
• Affects deep tissues.
• Forms hematomas.
• Less common in mucous membranes.
• Can affect joints, muscles, the central nervous system, and the retroperitoneal space.
• Clinical examples include liver disease affecting CF synthesis, factor deficiency, and acquired inhibitors.

Fibrinogen Group

• Factor I (Fibrinogen):
• Rarest to occur
• Inheritance pattern is autosomal recessive.
• Can cause afibrinogenemia or dysfibrinogenemia.
• Acquired coagulopathies include severe liver disease and DIC
• DIC is where CF are consumed during coagulation and clotting.
• Prolonged APTT and PT are corrected by adsorbed plasma, aged plasma, and fresh normal plasma, but not by fresh serum, aged serum, or adsorbed serum.
• Factor V (Proaccelerin):
• Inheritance pattern is autosomal recessive.
• Causes Owren's disease, labile factor deficiency, and parahemophilia.
• Fibrinolysis causes acquired coagulopathy.
• Prolonged APTT and PT are corrected by fresh normal and adsorbed plasma and are not corrected by aged plasma, fresh serum, aged serum or adsorbed serum.
• Factor VIII (Antihemophilic factor):
• Inheritance pattern is X-linked/sex-linked.
• Inflammatory diseases (which increase Factor VIII) cause acquired coagulopathy .
• Prolonged APTT is corrected by fresh normal and adsorbed plasma and is not corrected by aged plasma, fresh serum, aged serum or adsorbed serum.
• Factor XIII (Fibrin stabilizing factor):
• Inheritance pattern is autosomal recessive.
• Causes factor XIII deficiency.
• Prolonged APTT can be corrected by fresh normal and absorbed plasma and is not corrected by aged plasma, fresh serum, aged serum or adsorbed serum.

Prothrombin Group

• Factor II (Prothrombin):
• Least common to occur
• Inheritance is autosomal recessive.
• Causes prothrombin deficiency.
• Acquired coagulopathies include liver disease and vitamin K deficiency
• Vitamin K deficiency results in a functional deficiency because gamma carboxylation cannot occur, thus, factors cannot interact with calcium or bind to platelet phospholipids.
• Prolonged PT and APTT are corrected by fresh normal and aged plasma, but not by adsorbed or fresh serum.
• Factor VII (Proconvertin):
• Results in the most profound disorder observed
• The inheritance pattern is autosomal recessive.
• Causes Factor VII deficiency.
• Oral anticoagulants (warfarin, coumarin & caumadin) cause the acquired coagulopathy because they inhibit vit K.
• Prolonged PT is corrected by fresh normal and aged plasma, and is not corrected by fresh serum or adsorbed plasma.
• Factor IX (Plasma Thromboplastin/Christmas Factor):
• Inheritance pattern is X-linked/sex-linked.
• Causes Hemophilia B (Christmas disease).
• Bile duct obstruction causes acquired coagulopathy because vitamin K requires bile for complete digestion and proper absorption
• Obstruction leads to incomplete digestion and absorption of vitamin K.
• Prolonged APTT is corrected by fresh and aged normal plasma and is not corrected by adsorbed plasma or fresh serum.
• Factor X (Stuart-Prower):
• Inheritance is autosomal recessive
• Causes factor X deficiency
• Prolonged PT and APTT, and abnormal Stypven Time are corrected by fresh and aged normal plasma and is not corrected by adsorbed plasma or fresh serum.

Contact Group

• Factor XI (Plasma Thromboplastin Antecedent):
• Inheritance pattern is autosomal recessive.
• Causes Hemophilia C.
• Prolonged APTT is corrected by ALL.
• Factor XII (Hageman Factor/Glass Factor/Contact Factor):
• Inheritance pattern is autosomal recessive.
• Causes Factor XII/Hageman deficiency.
• Prolonged APTT is corrected by aged serum and adsorbed plasma.
• PK (Fletcher Factor):
• Inheritance pattern is autosomal recessive.
• Causes Fletcher trait.
• HMWK (Fitzgerald Factor):
• Inheritance pattern is autosomal recessive.
• Causes Fitzgerald trait
• Both PK and HMWK deficiencies cause prolonged APTT
• No correction reported

Hemophilia

• Deficiency in antihemophilic factors A, B, and C.
• Hemophilia A (Factor VIII deficiency):
  • Royal disease first recognized among the royal family of England.
  • Classic hemophilia.
  • It is a Sex-linked disorder.
  • The most common type occurs in 1 in 5,000 to 10,000 males.
  • The most severe congenital anomaly.
• Hemophilia B (Factor IX deficiency):
  • Christmas disease named after Stephen Christmas, the first boy discovered to have factor IX deficiency.
  • It is a Sex-linked disorder.
  • Occurs in 1 in 25,000 to 30,000 males.
  • Manifests with signs and symptoms similar to hemophilia A, but are milder.
• Hemophilia C (Factor XI deficiency):
  • Rosenthal syndrome.
  • It is Autosomal
  • Higher incidence in Ashkenazi Jews.
  • Often a silent type (not necessarily associated with a bleeding disorder).

Hemophilia Severity vs Factor Level and Manifestation

• Severe: <1% factor level results in spontaneous bleeding/bleeding with minor surgery/trauma
• Moderate: 1-5% factor level results in spontaneous bleeding being uncommon while surgical bleeding may happen
• Mild: 5-20% factor level results in no spontaneous bleeding, but may bleed with major surgery/trauma

Laboratory Testing for Hemophilia:

• Prolonged APTT test.

Hemophilia Treatment

• Hemophilia A: Commercial Factor VIII concentrate, Recombinant Factor VIII and DDAVP.
  • Avoid aspirin and analgesics.
• Hemophilia B: Commercial Factor IX concentrate, Recombinant Factor IX
• Hemophilia C: FFP/WHOLE BLOOD and No single blood component treatment.