- Venous Thrombosis
- Most common genetic risk
factor: activated protein C resistance
- frequency: 20% of
patients diagnosed with their
first deep venous thrombosis
- Relative risk:
8X-- heterozygotes; 80X in
homozygotes
- Acquired
Disease:
- increased
thromboembolism risk: associated
with arrhythmia
- long-term
proven efficacy of oral
anticoagulants in
management of chronic
atrial fibrillation
- increased
thromboembolism risk: associated
with prolonged bed rest (deep
venous thrombosis/embolism)
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- Antithrombotic Management:
- Prevention: Goal -- reduce
incident/mortality rate from
pulmonary embolism
- Heparin -- prevention of venous
thrombosis
- intermittent
administration (effective
prophylaxis) --
subcutaneous
- Oral Anticoagulants:
- generally
limited use due to
bleeding risk/laboratory
prothrombin time
monitoring
- effective
prophylaxis for patients
with:
- atrial
fibrillation
- prosthetic
heart valves
- Early
postoperative ambulation--
reducing venous stasis
- also
effective: external
pneumatic leg compression
- Enoxaparin (Lovenox)-- approved for
prophylaxis only in hip
replacement patients.
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- Venous Thrombosis -- established
- heparin & warfarin -- maximal dosages;
similar treatment for pulmonary
embolism
- small thrombi --
calf veins -- often managed
without anticoagulants
- In patients with
recurring thrombi and a positive
family history:
- evaluate for protein C or
protein S deficiency
- Antithrombin
III concentrate: maybe helpful
in deficient patients
- Heparin resistance
(associate with
antithrombin III
deficiency) -- overcome
with concentrate
- Note:since warfarin
crosses the placental barrier,
venous thromboembolic disease in
pregnant women: subcutaneous
heparin with mandatory monitoring
of anticoagulant effect.
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- Arterial Thrombosis:
- Clinical Uses:platelet-inhibiting agents
- management of
unstable angina, transient
ischemic attacks, strokes, acute
myocardial infarction
- in myocardial
infarction and angina, platelets
inhibiting drugs used in
combination with:
- beta-blockers
- calcium channel blockers
- fibrolytic agents
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Drugs
Used in Bleeding Disorders
- Vitamin K
- required for biological
activity of:
- prothrombin
- factors VII, IX, X
- fat-soluble, available
from diet & synthesized by human
intestinal bacteria
- Two natural forms:
- vitamin K1
- vitamin K2
- menaquinone,
found in human tissue,
bacterial synthesis
- Vitamins K1
and K2--
require bile salts for absorption from
intestinal tract
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- Clinical Issues:vitamin K
- Vitamin K1:
- given
to all newborns;
preventative of
hemorrhagic due to vitamin K deficiency
(common in premature
infants)
- Deficiency:
- hospitalized
patients (ICU) due to:
- poor
diet
- parenteral
nutrition
- recent
surgery
- multiple
antibiotic treatment
- uremia
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Plasma Fractions-- Bleeding due to factor
deficiencies
- Overview:factors
- Coagulation defects: primarily
--
- factor
VIII deficiency --classic
hemophilia (hemophilia A)
- factor IX
deficiency -- Christmas disease,
hemophilia B)
- concentrated
plasma fractions: available to
manage hemophilia A & B
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- Factor VIII:-- 2 preparations
- cryoprecipitate--
plasma protein fraction; derived
from whole blood
- hemophilia (factor VIII)
- von Willebrand's disease
- source of fibrinogen
(occasionally)
- must match Rh status,
i.e. RH-negative women
should receive only RH-negative
cryoprecipitate
- lyophilized
factor VIII concentrates:
- derived
from plasma pools
(cryoprecipitate from
individual donors,
probably safer)
- Reduced
danger of viral disease
(hepatitis B, hepatitis
C, HIV) transmission by:
- pasteurization
- ultraviolet
radiation
- Desmopressin acetate
(arginine vasopressin)
- increases
factor VIII activity in
patients with mild
hemophilia or von
Willebrand's disease.
- Clinically
used before minor surgery (e.g.,dental)
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- Factor
IX:
- Freeze-dried
plasma concentrates containing:
- prothrombin,
factor IX, factor X,
factor VII
- coagulation
factors may be activated
in manufacturing (heparin
may be added to inhibit
these factors)
- Fibrinogen:
- Forms: plasma,
factor VIII cryoprecipitate,
lyophilized factor VIII
concentrates.
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Fibrolytic Inhibitors:aminocaproic
acid
Serine Protease Inhibitors: Aprotinin
- Aprotinin:
- serine protease inhibitor
- inhibits
plasmin-streptokinase complex in patients
receiving this thrombolytic treatment
- Significant reduction in
bleeding in certain surgeries:
- currently approved
for patients undergoing coronary
artery bypass grafting in which
there is a high-risk for
excessive blood loss
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