Secondary hemostasis

DISORDERS OF SECONDARY HEMOSTASIS TYPICALLY PRESENT

DISORDERS OF SECONDARY
HEMOSTASIS TYPICALLY PRESENT
WITH DEEP TISSUE BLEEDING
WITH RE-BLEEDING AFTER SURGICAL PROCEDURES (E.G. DENTAL
BLEEDING INTO MUSCLES AND PROCEDURES
JOINTS VS PRIMARY HEMOSTASIS COAGULATION DISORDER PRESENTS
WAS SUPERFICIAL BLEEDING WITH RECURRENT
HEMARTHROSES, SPONTANEOUS / EASY BRUISING,
AND BLEEDING AFTER SURGERY)
Thrombin
• The coagulation
cascade generates thrombin
(factor IIa), which
converts fibrinogen in the
platelet plug to fibrin (factor Ia)
• Thrombin also activates IIa
(itself), V, VIII, and XI
Factor 13

• After fibrin is formed from fibrinogen, it

is cross-linked by factor XIII yielding
a stable platelet-fibrin thrombus
• A factor XIII deficiency causes
spontaneous or excessive bleeding, but
does NOT prolong BT, PT, PTT, OR TT
Activation of Coagulation
cascade
• Factors of the coagulation cascade are
produced by the liver in
an inactive state
• Activation of the coagulation
cascade requires
the phospholipid surface of platelets
• also requires Ca2+ from platelet dense
granules derived from platelet dense
granules
 Activation of Coagulation
cascade

• Tissue thromboplastin activates factor

VII, which initiates the extrinsic
pathway of the coagulation cascade
• Subendothelial
collagen activates factor XII, which
initiates the intrinsic pathway of the
coagulation cascade
 Hemophilia's X-linked recessive

• Hemophilia A can arise from a(n) new (denovo) mutation without any
family history (20%)
• Hemophilia (A, B, C) presents with normal bleeding time and platelet
count
• Hemophilia (A, B, C) presents with normal PT and increased PTT

Hemophilia B (Christmas disease) is a coagulation disorder due to a

genetic factor IX deficiency

Hemophilia C is a coagulation disorder due to a genetic factor XI deficiency

Treatment of hemophilia A involves desmopressin plus recombinant factor

VIII
-hemophilia B and C are treated similarly with recombinants to their respective
factor deficiencies
 Coagulation factor
inhibitor
• A coagulation factor inhibitor is
a(n) acquired antibody against a coagulation
factor, resulting in impaired factor function
• Anti-Factor VIII: most common coagulation
factor inhibitor presents similarly to hemophilia
A
• A coagulation factor inhibitor is
a(n) acquired antibody against a coagulation
factor, resulting in impaired factor function
Correcting study
• In hemophilia A,
mixing normal plasma with the
patient's plasma (mixing
study) does correct the PTT
• normal plasma replaces the
deficient fac
Fixing study when it’s d.t coagulation factor
inhibitor
• factor VIII coagulation factor
inhibitor, mixing normal plasma
with a patient's
plasma doesn't correct the PTT
• the coagulation factor inhibitor
inhibits the factor VIII in the
normal plasma --> NO
CORRECTION
 Vitamin K deficiency
•Vitamin K is activated by the
enzyme epoxide reductase in the liver
oxidized vitamin K (inactive) --> reduced
vitamin K (active)
•Activated vitamin K acts as a co-factor for the enzyme γ-
glutamyl carboxylase
•deficiency may occur in newborns due to lack of colonic
bacteria that normally synthesize vitamin K
• deficiency may occur due to long-
term antibiotic therapy, which disrupts the gut flora
•deficiency may occur due to fat malabsorption, which
leads to deficiency of fat-soluble vitamins
•Vitamin K deficiency presents with normal bleeding time
•Vitamin K deficiency presents
with increased PT and increased (in severe cases) PTT
• Vitamin K deficiency is essentially acts like a patient
with warfarin; PTT is less sensitive than PT (since VII
levels drop first)
 • Abnormal secondary hemostasis may occur due
to liver failure, which
causes decreased production of coagulation
factors and decreased activation of vitamin K:
epoxide reductase is found in the liver
• Abnormal secondary hemostasis may occur due
to large-volume transfusion, which dilutes
coagulation factors, resulting in a relative deficiency

Vitamin K • Vitamin K is necessary for gamma carboxylation of

factors II, VII, IX, X, and proteins C and S
• gamma carboxylation gives coagulation factors
a Ca2+ binding site
• Warfarin inhibits vitamin K, which produces factor X,
a shared coagulation factor to both intrinsic and
extrinsic pathways. (intercom INR)